Acylated 1,2,3,4-tetrahydronaphthyl amines and their use as pharmaceutical agents

ABSTRACT

The present invention relates to compounds of general formula (I), 
                 
 
wherein R 1 -R 4  have the meanings given in the specification, A is CH2, CHOH or CH—(C 1 -C 3 -alkyl), B and C are independently CH 2  or CH—(C 1 -C 3 -alkyl), and R 5  is an aryl or heteroaryl group optionally substituted by the substituents listed in the specification. The compounds are useful for the manufacture of medicaments for the treatment of cardiovascular diseases, stable or unstable angina pectoris, coronary heart disease, Prinzmetal angina, acute coronary syndrome, heart failure, myocardial infarction, stroke, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, restenosis, endothelial damage after PTCA, hypertension, essential hypertension, pulmonary hypertension, secondary hypertension, renovascular hypertension, chronic glomerulonephritis, erectile dysfunction, ventricular arrhythmia, diabetes or diabetes complications, nephropathy or retinopathy, angiogenesis, asthma bronchiale, chronic renal failure, cirrhosis of the liver, osteoporosis, and restricted memory performance or a restricted ability to learn, or the lowering of cardiovascular risk of postmenopausal women or after intake of contraceptives.

The present invention relates to acylated 1,2,3,4-tetrahydronaphthylamines of the general formula (I), with the definitions of R¹ to R⁵ andA, B and C given below in the text, in any of their stereoisomeric formsor mixtures thereof in any ratio or the pharmaceutically acceptablesalts thereof and their use as pharmaceutical agents.

Endothelial NO synthase (eNOS, NOS-III) belongs to a group of threeisoenzymes which produce nitric oxide (NO) by oxidation of arginine.Endothelially released NO is of central importance in a number of keycardiovascular mechanisms. It has a vasodilating effect and inhibits theaggregation of platelets, the adhesion of leukocytes to the endotheliumand the proliferation of intimal smooth muscle cells.

Endothelial NO synthase is subject to physiological andpathophysiological regulation both at the transcriptional and at thepost-transcriptional level. Enzyme already present in the endotheliummay undergo calcium-dependent and calcium-independent activation throughphosphorylation of specific amino acids, but also by direct interactionswith specific proteins. Stimulators of this, usually transient, NOrelease are, extracellular arginine, 17β-estrogen and the mechanicalstimulus exerted on the luminal surface of the endothelium by the bloodflow (shear stress). The latter additionally leads to regulation of eNOSat the transcriptional level. Thus, for example, Sessa et al. (Circ.Research 74 (1994) 349-353) were able by means of exercise training andthe increase in shear stress associated therewith to obtain a markedincrease in ecNOS.

Whether regulation at the post-transcriptional level is relevant invivo, is not unambiguously proved. Thus, for example, administration ofa high arginine dose is followed by only a transient improvement in theendothelium-dependent vasorelaxation in patients with coronary heartdisease.

On the other hand, the significance of the upregulation of the eNOSprotein is scientifically accepted. Thus, there are findings which showthat the protective properties of the HMG-CoA reductase inhibitorsimvastatin can be attributed, besides the lipid lowering, also in partto an increase in eNOS expression in vivo (Endres et al., Proc. Natl.Acad. Sci. USA 95 (1998) 8880-8885). It is additionally known thatsingle point mutations in the 5′-flanking region of the eNOS gene (“eNOSpromoter”), and the reduction in the rate of eNOS gene transcriptionassociated therewith, in the Japanese population is associated with anincrease in the risk of coronary spasms (Nakayama et al., Circulation 99(1999) 2864-2870).

The current assumption therefore is that the transcriptional andpost-transcriptional mechanisms of eNOS regulation are seriouslydisturbed in a large number of disorders, especially in cardiovasculardisorders. Even in very early stages of a wide variety of cardiovasculardisorders it is possible for a dysfunction of this type in theendothelium lining the blood vessels to lead to a deficiency ofbioactive NO, which is manifested as the disorder progresses in the formof measurable pathophysiological and morphological disorder progressesin the form of measurable pathophysiological and morphological changes.Thus, critical steps in early atherogenesis are speeded up by a decreasein endothelial NO release, such as, for example, the oxidation of lowdensity lipoproteins, the recruitment and deposition of monocytes in theintima of vessels, and the proliferation of intimal cells. A consequenceof atherogenesis is the formation of plaques on the inside of the bloodvessels, which may in turn lead, through a diminution in the shearstress, to a further decrease in endothelial NO release and a furtherdeterioration in the pathology. Since endothelial NO is also avasodilator, a decrease thereof frequently also leads to hypertension,which may, as an independent risk factor, cause further organ damage.

The aim of a therapeutic approach to the treatment of these disordersmust accordingly be to interrupt this chain of events by increasing theendothelial NO expression. Gene transfer experiments which lead in vitroto overexpression of NO synthase in previously damaged vessels are infact able to counteract the described processes and are thus evidence ofthe correctness of this approach (Varenne et al., Hum. Gene Ther. 11(2000) 1329).

Some low molecular weight compounds which, in cell cultures, may lead toa direct effect on eNOS transcription and expression are disclosed inthe literature. The statins which have already been mentioned are,however, the only substances for which it has been possible to date toshow such an increase in eNOS in vivo as a side effect. In view of theknown range of side effects of this class of substances, however, it isunclear how far this effect is present in a toxicologicallyunproblematic dose.

Liao et al. claim in WO 99/47153 and WO 00/03746 the use of rhoGTPaseinhibitors and agents which influence the organization of the actincytoskeleton for increasing eNOS in endothelial cells and for thetherapy of various disorders such as, for example, strokes or pulmonaryhypertension, without, however, indicating a specific way of achievingthis.

Thus, there exists a strong need for compounds which upregulateeNOS-expression in endothelial cells. The object of the presentinvention is to provide compounds showing this ability.

This object is attained by acylated 1,2,3,4-tetrahydronaphthyl aminesaccording to the general formula (I) in any of their stereoisomericforms or mixtures thereof in any ratio or the pharmaceuticallyacceptable salts thereof.

In the above formula (I),

R¹ and R⁴ are independently of each other selected from the groupconsisting of: H; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents ofwhich are selected from the group consisting of F, OH, C₁-C₈-alkoxy,(C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, and unsubstituted and atleast monosubstituted phenyl and heteroaryl, the substituents of whichare selected from the group consisting of halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which areselected from the group consisting of halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁹CO; CONR¹⁰R¹¹; COOR¹²; CF₃;halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵; S(O)_(m)R¹⁶; SO²NR¹⁷R¹⁸; andNO₂;

R² and R³ are independently from each other selected from the groupconsisting of: H; halogens; pseudohalogens; unsubstituted and at leastmonosubstituted C₁-C₁₀-alkyl the substituents of which are selected fromthe group consisting of OH, phenyl, and heteroaryl; OH; C₁-C₁₀-alkoxy;phenoxy; S(O)_(m)R¹⁹; CF₃; CN; NO₂; (C₁-C₁₀-alkyl)amino;di(C₁-C₁₀-alkyl)amino; (C₁-C₆-alkyl)-CONH—; unsubstituted and at leastmonosubstituted phenyl-CONH— and phenyl-SO₂—O—, the substituents ofwhich are selected from the group consisting of halogens,pseudohalogens, CH₃ and methoxy; (C₁-C₆-alkyl)SO₂—O—, unsubstituted andat least monosubstituted (C₁-C₆-alkyl)CO, the substituents, of which areselected from the group consisting of F, di(C₁-C₃-alkyl)amino,pyrrolidinyl and piperidinyl; and phenyl-CO, the phenyl part of whichcan be substituted by one or more substituents from the group consistingof C₁-C₃-alkyl, halogens and methoxy;

A is selected from the group consisting of CH₂, CHOH andCH—(C₁-C₃-alkyl);

B is selected from the group consisting of CH₂ and CH—(C₁-C₃-alkyl);

C independently has the same meaning as B;

R⁵ is a group Hetar which can be unsubstituted or carry one or moresubstituents selected from the group consisting of: halogens;pseudohalogens; NH₂; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, C₁-C₁₀-alkoxy,(C₁-C₁₀-alkyl)amino, di(C₁-C₁₀-alkyl)amino, the substituents of whichare selected from the group consisting of F, OH, C₁-C₈-alkoxy, aryloxy,(C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl; aryl- orheteroaryl-substituted C₁-C₄-alkyl; CF₃; NO₂; OH; phenoxy; benzyloxy;(C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH; phenylamino; benzylamino;(C₁-C₁₀-alkyl)-CONH—; (C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR 24R²⁵; R²⁶SO₂NH—; R²⁷SO₂N(C₁-C₆-alkyl)-; andsaturated or at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms selected from thegroup consisting of N, O and S, which heterocycles can be substituted byone or more substituents selected from the group consisting of halogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, where said heterocycles canoptionally be condensed to the said group Hetar; wherein all aryl,heteroaryl, phenyl, aryl-containing, heteroaryl-containing andphenyl-containing groups, which are optionally present in the saidsubstituents of the said group Hetar, can be substituted by one or moresubstituents selected from the group consisting of halogens,pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;

R⁶ is selected from the group consisting of:

-   H; C₁-C₁₀-alkyl, which can be substituted by one or more    substituents selected from the group consisting of F, C₁-C₈-alkoxy,    and di(C₁-C₈-alkyl)amino; aryl-(C₁-C₄-alkyl) and    heteroaryl-(C₁-C₄-alkyl), which can be substituted by one or more    substituents selected from the group consisting of halogens,    C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino;

R⁷ is selected from the group consisting of:

-   H; C₁-C₁₀-alkyl which can be substituted by one or more substituents    selected from the group consisting of F, C₁-C₈-alkoxy,    di(C₁-C₈-alkyl)amino and phenyl; phenyl; indanyl; and heteroaryl;    and wherein each of the aforementioned aromatic groups can be    unsubstituted or carry one or more substituents from the group    consisting of halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy    and CF₃;

R⁸ is H or C₁-C₁₀-alkyl;

R⁹ is selected from the group consisting of: C₁-C₁₀-alkyl which can beunsubstituted or carry one or more substituents from the groupconsisting of: F, (C₁-C₄)-alkoxy, di(C₁-C₃-alkyl)amino; andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are selected from the group consisting ofC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃;

R¹⁰ independently has the same meaning as R⁷;

R¹¹ independently has the same meaning as R⁸;

R¹² independently has the same meaning as R⁶;

R¹³ is selected from the group consisting of: H; C₁-C₆-alkyl;unsubstituted and substituted phenyl, benzyl, heteroaryl,(C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, the substituents ofwhich are selected from the group consisting of halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one ormore of these substituents can be present;

R¹⁴ independently has the same meaning as R¹³;

R¹⁵ is selected from the group consisting of: H; C₁-C₁₀-alkyl;(C₁-C₃-alkoxy)-C₁-C₃-alkyl; and substituted and unsubstituted benzyl,phenyl and heteroaryl, the substituents of which are selected from thegroup consisting of halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy,and CF₃, and wherein one or more of these substituents can be present;

R¹⁶ is selected from the group consisting of: C₁-C₁₀-alkyl which can besubstituted by one or more substituents selected from the groupconsisting of F, OH, C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto,(C₁-C₈-alkyl)amino and di(C₁-C₈-alkyl)amino; CF₃; and substituted andunsubstituted phenyl and heteroaryl, the substituents of which areselected from the group consisting of halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one or more of thesesubstitutents can be present;

R¹⁷ independently has the same meaning as R⁷;

R¹⁸ independently has the same meaning as R⁸;

R¹⁹ independently has the same meaning as R¹⁶;

R²⁰ independently has the same meaning as R¹⁶;

R²¹ independently has the same meaning as R⁶;

R²² independently has the same meaning as R⁷;

R²³ independently has the same meaning as R⁸;

R²⁴ independently has the same meaning as R⁷;

R²⁵ independently has the same meaning as R⁸;

R²⁶ independently has the same meaning as R¹⁶;

R²⁷ independently has the same meaning as R¹⁶;

heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms selected from the groupconsisting of N, O and S;

the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms selected from the groupconsisting of N, O and S;

aryl is phenyl, naphth-1-yl or naphth-2-yl; and

m is 0, 1 or 2;

with the proviso that, in case R¹, R², R³ and R⁴ are hydrogen or one ofthe substituents, R¹, R², R³ or R⁴ is C₁-C₆-alkoxy, R⁵ is notunsubstituted pyridyl or unsubstituted or substituted 4-oxoquinolinyl.

If, in the compounds of formula (I), groups or substituents such as, forexample, aryl, heteroaryl, alkyl etc., can be present several times,they all independently from each other have the meanings indicated andcan hence, in each individual case, be identical with or different fromeach other. One example is the di(C₁-C₁₀-alkyl)amino group in which thealkyl substitutents can be identical or different.

Alkyl, alkenyl and alkynyl residues can be linear or branched, acyclicor cyclic. This also applies when they are part of other groups, forexample in alkoxy groups, alkoxycarbonyl groups or amino groups, or whenthey are substituted.

Examples for alkyl groups are methyl, ethyl, propyl, butyl, pentyl,hexyl, heptyl, octyl, nonyl, decyl, the n-isomers of these residues,isopropyl, isobutyl, isopentyl, sec-butyl, tert-butyl, neopentyl,3,3-dimethylbutyl. The term alkyl here also expressly includescycloalkyl residues and cycloalkyl-alkyl-residues (alkyl substituted bycycloalkyl) containing at least three carbon atoms. Examples for suchcycloalkyl residues are cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl and cyclooetyl. All cycloalkyl groups can besubstituted by one or more identical or different (C₁-C₄)-alkylresidues, in particular by methyl. Examples for substituted cycloalkylresidues are 4-methylcyclohexyl, 4-tert-butylcyclohexyl or2,3-dimethylcyclopentyl. Furthermore, unless stated otherwise, the termalkyl here also includes unsubstituted alkyl residues as well as alkylresidues which are substituted by one or more, for example one, two,three or four, identical or different residues, for example, arylgroups. In substituted alkyl residues, for example arylalkyl,hydroxyalkyl such as —(C₁-C₃)-alkyl-OH or alkoxyalkyl such as—(C₁C₃)-alkyl-O—(C₁-C₄)-alkyl, the substituents can be present in anydesired position.

Examples for alkenyl and alkynyl groups are the vinyl residue, the1-propenyl residue, the 2-propenyl residue (allyl residue), the2-butenyl residue, the 2-methyl-2-propenyl residue, the3-methyl-2-butenyl residue, the ethynyl residue, the 2-propynyl residue(propargyl residue), the 2-butynyl residue or the 3-butynyl residue. Theterm alkenyl here also expressly includes cycloalkenyl residues andcycloalkenyl-alkyl-residues (alkyl substituted by cycloalkenyl)containing at least three carbon atoms. Examples for cycloalkenylresidues are cyclopentenyl, cyclohexenyl, cycloheptenyl andcyclooctenyl. All cycloalkenyl groups can be substituted by one or moreidentical or different (C₁-C₄)-alkyl residues, in particular by methyl.Furthermore, unless stated otherwise, the term alkenyl and alkynyl herealso includes unsubstituted alkenyl and alkynyl residues as well asalkenyl and alkynyl residues which are substituted by one or more, forexample one, two, three or four, identical or different residues, forexample aryl groups. In substituted alkenyl and alkynyl residues, forexample, arylalkenyl, hydroxyalkenyl such as —(C₂-C₃)alkenyl-OH oralkoxyalkenyl such as (C₁-C₃-alkyl)-O—(C₂-C₄-alkenyl)-, the substituentscan be present in any desired position.

Examples for C₃-C₅-alkandiyl are —CH₂CH₂CH₂—, —CH₂—CH(CH₃),—CH₂CH₂CH₂CH₂— and —CH₂CH₂CH₂CH₂CH₂— groups.

If not stated otherwise, the above-mentioned phenyl residues, naphthyland indanyl residues and heterocyclic residues (including heteroarylresidues) can be unsubstituted or can carry one or more, for exampleone, two, three or four, of the substituents indicated in the abovedefinition which can be in any desired position. If in compounds of theformula (I) nitro groups are present as substituents, in total only upto two nitro groups are preferably present in the molecule. Inmonosubstituted phenyl residues the substituent can be in the2-position, the 3-position or the 4-position, in disubstituted phenylresidues the substituents can be in 2,3-position, 2,4-position,2,5-position, 2,6-position, 3,4-position or 3,5-position. Intrisubstituted phenyl residues the substituents can be in2,3,4-position, 2,3,5-position, 2,3,6-position, 2,4,5-position,2,4,6-position or 3,4,5-position. In fourfold substituted phenylresidues, the substituents can be in the 2,3,4,5-position, the2,3,4,6-position, or the 2,3,5,6-position. Tolyl (=methylphenyl) can be2-tolyl, 3-tolyl or 4-tolyl. Naphthyl can be 1-naphthyl or 2-naphthyl.In monosubstituted 1-naphthyl residues the substituent can be in the2-position, the 3-position, the 4-position, the 5-position, the6-position, the 7-position or the 8-position; in monosubstituted2-naphthyl residues in the 1-position, the 3-position, the 4-position,the 5-position, the 6-position, the 7-position or the 8-position. Inhigher substituted naphthyl radicals, for example 1-naphthyl radicals or2-naphthyl radicals which carry two or three substituents, thesubstituents can also be situated in all possible positions. Indanylresidues include indan-1-yl residues and indan-2-yl residues which canbe unsubstituted or carry one or more of the substituents indicated. Incase the indanyl residues are substituted, the substituent orsubstituents can be in any of the positions possible.

The above definitions as well as the following definitions relating tomonovalent residues equally apply to the divalent residues phenylene,naphthylene and heteroarylene. Those divalent residues can be attachedto the adjacent groups by any ring carbon atom. In the case of aphenylene residue, these can be in 1,2-position (ortho-phenylene),1,3-position (meta-phenylene) or 1,4-position (para-phenylene). In thecase of a naphthylene residue the free bonds can be in 1,2-position(=1,2-naphthylene or 1,2-naphthalinediyl) or in 1,3position,1,4-position, 1,5-position, 1,6-position, 1,7-position, 1,8-position,2,3-position, 2,6-position or 2,7-position. In the case of 5-memberedring aromatics containing one heteroatom such as, for example, thiopheneor furan, the two free bonds can be in 2,3 position, 2,4-position,2,5-position or 3,4-position. A divalent residue derived from pyridinecan be a 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-pyridinediyl residue. Inthe case of unsymmetrical divalent residues, the present inventionincludes all positional isomers, i.e., in the case of a 2,3-pyridinediylresidue, for example, it includes the compound in which the one adjacentgroup is present in the 2-position and the other adjacent group ispresent in the 3-position as well as the compound in which the oneadjacent group is present in the 3-position and the other adjacent groupis present in the 2-position.

Unless stated otherwise, heteroaryl residues, heteroarylene residues,heterocyclyl residues and rings which are formed by two groups bonded toa nitrogen are preferably derived from heterocycles which contain one,two, three or four heteroatoms which can be identical or different; morepreferably they are derived from heterocycles which contain one, two, orthree, in particular one or two, heteroatoms which can be identical ordifferent. Unless stated otherwise, the heterocycles can be monocyclicor polycyclic, for example monocyclic, bicyclic or tricyclic. Preferablythey are monocyclic or bicyclic. The rings preferably are 5-memberedrings, 6-membered rings or 7-membered rings. Examples of monocyclic andbicyclic heterocyclic systems from which residues occurring in thecompounds of the formula (I) can be derived, are pyrrole, furan,thiophene, imidazole, pyrazole, 1,2,3-triazole, 1,2,4-triazole,1,3-dioxole, 1,3-oxazole (=oxazole), 1,2-oxazole (=isoxazole),1,3-thiazole (=thiazole), 1,2-thiazole (=isothiazole), tetrazole,pyridine, pyridazine, pyrimidine, pyrazine, pyran, thiopyran,1,4-dioxine, 1,2-oxazine, 1,3-oxazine, 1,4-oxazine, 1,2-thiazine,1,3-thiazine, 1,4-thiazine, 1,2,3-triazine, 1,2,4-triazine,1,3,5-triazine, 1,2,4,5-tetrazine, azepine, 1,2-diazepine,1,3-diazepine, 1,4-diazepine, 1,3-oxazepine, 1,3-thiazepine, indole,benzothiophene, benzofuran, benzothiazole, benzimidazole, benzodioxol,quinoline, isoquinoline, cinnoline, quinazoline, quinoxaline,phthalazine, thienothiophenes, 1,8-naphthyridine and othernaphthyridines, pteridin, or phenothiazine, each of them in saturatedform (perhydro form) or in partially unsaturated form (for example inthe dihydro form or the tetrahydro form) or in maximally unsaturatedform, in case the respective forms are known and stable. The term “aryl”and the term “heteroaryl” as used herein comprise bicyclic residues inwhich both cycles are aromatic as well as bicyclic residues in whichonly one cycle is aromatic. Independently, the same applies to the term“group Ar” or the term “group Hetar”, respectively. Suitableheterocycles include, for example, for example, the saturatedheterocycles pyrrolidine, piperidine, piperazine, morpholine andthiomorpholine. The degree of saturation of heterocyclic groups isindicated in their individual definitions. Unsaturated heterocycles cancontain, for example, one, two or three double bonds within the ringsystem. 5-membered rings and 6-membered rings can in particular also bearomatic.

Substituents which may be derived from these heterocycles can beattached via any suitable carbon atom. Residues derived from nitrogenheterocycles can carry a hydrogen atom or a substituent on a ringnitrogen atom, and examples include pyrrole, imidazole, pyrrolidine,morpholine, piperazine residues, etc. Those nitrogen heterocyclicresidues can also be attached via a ring nitrogen atom, in particular ifthe respective heterocyclic residue is bonded to a carbon atom. Forexample, a thienyl residue can be present as 2-thienyl residue or3-thienyl residue, a furyl residue as 2-furyl residue or 3-furylresidue, a pyridyl residue as 2-pyridyl residue, 3-pyridyl residue or4-pyridyl residue, a piperidinyl residue as 1-piperidinyl residue(=piperidino residue), 2-piperidinyl residue, 3-piperidinyl residue or4-piperidinyl residue, a (thio)morpholinyl residue as2-(thio)morpholinyl residue, 3-(thio)morpholinyl residue or4-(thio)morpholinyl residue (=thiomorpholino residue). A residue derivedfrom 1,3-thiazole or imidazole which is attached via a carbon atom canbe attached via the 2-position, the 4-position or the 5-position.

In case a heterocyclic group is substituted, it can carry one or more,for example one, two, three or four, identical or differentsubstituents. Substituents in heterocycles can be present in any desiredpositions, for example in a 2-thienyl residue or 2-furyl residue in the3-position and/or in the 4-position and/or in the 5-position, in a3-thienyl residue or 3-furyl residue in the 2-position and/or in the4-position and/or in the 5-position, in a 2-pyridyl residue in the3-position and/or in the 4-position and/or in the 5-position and/or inthe 6-position, in a 3-pyridyl residue in the 2-position and/or in the4-position and/or in the 5-position and/or in the 6-position, in a4-pyridyl residue in the 2-position and/or in the 3-position and/or inthe 5-position and/or in the 6-position. Suitable nitrogen heterocyclescan also be present as N-oxides or as quarternary salts containing acounterion which is derived from a pharmaceutically acceptable acid.Pyridyl residues, for example, can be present as pyridine-N-oxides.

Halogen is fluorine, chlorine, bromine or iodine, preferably fluorine orchlorine.

Examples for pseudohalogens are CN and N₃, a preferred pseudohalogen isCN.

The present invention includes all stereoisomeric forms of the compoundsof the formula (I). Centers of asymmetry that are present in thecompounds of formula (I) all independently of one another have Sconfiguration or R configuration. The invention includes all possibleenantiomers and diastereomers and mixtures of two or more stereoisomers,for example mixtures of enantiomers and/or diastereomers, in all ratios.Thus, compounds according to the present invention which can exist asenantiomers can be present in enantiomerically pure form, both aslevorotatory and as dextrorotatory antipodes, in the form of racematesand in the form of mixtures of the two enantiomers in all ratios. In thecase of a cis/trans isomerism the invention includes both the cis formand the trans form as well as mixtures of these forms in all ratios. Allthese forms are an object of the present invention. The preparation ofindividual stereoisomers can be carried out, if desired, by separationof a mixture by customary methods, for example by chromatography orcrystallization, by the use of stereochernically uniform startingmaterials for the synthesis or by stereoselective synthesis. Optionallya derivatization can be carried out before a separation ofstereoisomers. The separation of a mixture of stereoisomers can becarried out at the stage of the compounds of the formula (I) or at thestage of an intermediate during the synthesis. The present inventionalso includes all tautomeric forms of the compounds of formula (I).

In case the compounds according to formula (I) contain one or moreacidic or basic groups, the invention also comprises their correspondingpharmaceutically or toxicologically acceptable salts, in particulartheir pharmaceutically utilizable salts. Thus, the compounds of theformula (I) which contain acidic groups can be present on these groupsand can be used according to the invention, for example, as alkali metalsalts, alkaline earth metal salts or as ammonium salts. More preciseexamples of such salts include sodium salts, potassium salts, calciumsalts, magnesium salts or salts with ammonia or organic amines such as,for example, ethylamine, ethanolamine, triethanolamine or amino acids.Compounds of the formula (I) which contain one or more basic groups,i.e. groups which can be protonated, can be present and can be usedaccording to the invention in the form of their addition salts withinorganic or organic acids.

Examples for suitable acids include hydrogen chloride, hydrogen bromide,phosphoric acid, sulfuric acid, nitric acid, methanesulfonic acid,p-toluenesulfonic acid, naphthalenedisulfonic acids, oxalic acid, aceticacid, tartaric acid, lactic acid, salicylic acid, benzoic acid, formicacid, propionic acid, pivalic acid, diethylacetic acid, malonic acid,succinic acid, pimelic acid, fumaric acid, maleic acid, malic acid,sulfaminic acid, phenylpropionic acid, gluconic acid, ascorbic acid,isonicotinic acid, citric acid, adipic acid, and other acids known tothe person skilled in the art.

If the compounds of the formula (I) simultaneously contain acidic andbasic groups in the molecule, the invention also includes, in additionto the salt forms mentioned, inner salts or betaines (zwitterions). Therespective salts according to the formula (I) can be obtained bycustomary methods which are known to the person skilled in the art as,for example, by contacting these with an organic or inorganic acid orbase in a solvent or dispersant, or by anion exchange or cation exchangewith other salts.

The present invention also includes all salts of the compounds of theformula (I) which, owing to low physiological compatibility, are notdirectly suitable for use in pharmaceuticals but which can be used, forexample, as intermediates for chemical reactions or for the preparationof pharmaceutically acceptable salts.

The present invention furthermore includes all solvates of compounds ofthe formula (I), for example hydrates or adducts with alcohols, activemetabolites of the compounds of the formula (II), and also derivativesand prodrugs of the compounds of the formula (I) which containphysiologically tolerable and cleavable groups, for example esters,amides and compounds in which the N—H group depicted in formula (I) isreplaced with an N-alkyl group, such as N-methyl, or with an N-acylgroup, such as N-acetyl or N-argininyl, including pharmaceuticallyacceptable salts formed on functional groups present in the Nacyl group.

Preferred compounds of the formula (I) are those compounds in which oneor more, including all, of the residues contained therein have themeanings given below, with all combinations of preferred substituentdefinitions being a subject of the present invention. With respect toall preferred compounds of the formula (I) the present invention alsoincludes all stereoisomeric forms and mixtures thereof in all ratios,and their pharmaceutically acceptable salts.

In preferred embodiments of the present invention, the substituents R¹to R⁵, A, B and C and the groups aryl and heteroaryl of the formula (I)independently of each other have the following meanings. Hence, one ormore of the substituents R¹ to R⁵ and A, B and C can have the preferredmeanings, the more preferred meanings, the even more preferred meanings,the most preferred meanings, or the particularly preferred meaningsgiven below.

R¹ is preferably selected from the group consisting of: H; C₁-C₄-alkyl;C₁-C₄-alkoxy; CF₃; halogens; pseudohalogens; (C₁-C₄-alkyl)-S(O)_(m)—;and unsubstituted and at least monosubstituted phenyl and heteroaryl,the substituents of which are selected from the group consisting ofhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, whereheteroaryl is selected from the group consisting of 5- and 6-memberedheterocycles containing one or more heteroatoms selected from the groupconsisting of N, O, and S; R¹ is more preferably H, halogen orC₁-C₄-alkyl.

R² is preferably selected from the group consisting of: H; halogens;pseudohalogens; and C₁-C₃-alkyl; R² is more preferably H.

R³ is preferably selected from the group consisting of: H; halogens;pseudohalogens; and C₁-C₃-alkyl; R³ is more preferably H.

R⁴ is preferably selected from the group consisting of: —H; C₁-C₄-alkyl;C₁-C₄-alkoxy; CF₃; halogens; pseudohalogens; (C₁-C₄-alkyl)-S(O)_(m)—;and unsubstituted and at least monosubstituted phenyl and heteroaryl,the substituents of which are selected from the group consisting ofhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, whereheteroaryl is selected from the group consisting of 5- and 6-memberedheterocycles containing one or more heteroatoms selected from the groupconsisting of N, O, and S; R⁴ is more preferably H, halogen orC₁-C₄-alkyl; R⁴ is most preferably H.

R¹ to R⁴ are in particular each H.

A is preferably selected from the group consisting of CH₂ and CHOH; A isin particular CH₂.

B and C are preferably independently of each other selected from thegroup consisting of CH₂ and CH—CH₃; more preferably B is a CH₂ unitwhile C is CH₂ or CH—CH₃; Most preferably B and C are CH₂.

R⁵ is preferably a group Hetar which can be unsubstituted or carry oneor more substituents selected from the group consisting of: halogens;CN; NH₂; unsubstituted and at least monosubstituted C₁-C₈-alkyl,C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₁-C₈-alkoxy, (C₁-C₈-alkyl)amino,di(C₁-C₈-alkyl)amino, the substituents of which are selected from thegroup consisting of F, C₁-C₆-alkoxy, phenoxy, (C₁-C₆-alkyl)mercapto,NH₂, (C₁-C₆-alkyl)amino, and di(C₁-C₆-alkyl)amino; C₃-C₅-alkandiyl;phenyl; heteroaryl; phenyl- or heteroaryl-substituted C₁-C₂-alkyl; CF₃;OH; phenoxy; benzyloxy; (C₁-C₆-alkyl)COO; S(O)_(m)(C₁-C₆)-alkyl;S(O)_(m)-phenyl; S(O)_(m)-heteroaryl; SH; phenylamino; benzylamino;(C₁-C₆-alkyl)-CONH—; (C₁-C₆-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-, heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₆-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—;COO(C₁-C₆alkyl); —CONH₂; —CONH(C₁-C₆-alkyl); —CON(di(C₁-C₆-alkyl));CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₆-alkyl); —SO₂NH(phenyl);—SO₂N(di(C₁-C₆-alkyl)); (C₁-C₆-alkyl)SO₂NH—;(C₁-C₆-alkyl)SO₂N(C₁-C₆-alkyl)-; phenyl-SO₂NH—;phenyl-SO₂N(C₁-C₆-alkyl)-; heteroaryl-SO₂NH—;heteroaryl-SO₂N(C₁-C₆-alkyl)-; and saturated or at least monounsaturatedaliphatic, mononuclear 5- to 7-membered heterocycles containing 1 to 3heteroatoms selected from the group consisting of N, O, and S, whichheterocycles can be substituted by one or more substituents selectedfrom the group consisting of halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH,oxo and CF₃, where said heterocycles can optionally be condensed to thesaid group Ar or the said group Hetar; wherein all heteroaryl, phenyl,heteroaryl-containing and phenyl-containing groups, which are optionallypresent in the said substituents of the said group Ar or the said groupHetar, can be substituted by one or more substituents selected from thegroup consisting of halogens, pseudohalogens, C₁-C₃-alkyl, OH,C₁-C₃-alkoxy, and CF₃;

R⁵ is more preferably a group Hetar which can be unsubstituted or carryone or more substituents selected from the group consisting of:halogens; CN; NH₂; unsubstituted and at least monosubstitutedC₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₃-alkoxy,(C₁-C₄alkyl)amino, di(C₁-C₄-alkyl)amino, the substituents of which areselected from the group consisting of F, C₁-C₃-alkoxy,(C₁-C₃-alkyl)mercapto, and NH₂; C₃-C₅-alkandiyl; phenyl; heteroaryl;phenyl- or heteroaryl-substituted C₁-C₂-alkyl; CF₃; OH;(C₁-C₄-alkyl)COO; S(O)_(m)(C₁-C₄)-alkyl; (C₁-C₄-alkyl)-CONH—;(C₁-C₄-alkyl)-CON(C₁-C₄-alkyl)-; (C₁-C₄alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—;COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl));CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂NH(phenyl);—SO₂N(di(C₁-C₄-alkyl)); (C₁-C₄-alkyl)SO₂NH—;(C₁-C₄-alkyl)SO₂N(C₁-C₄-alkyl)-; and saturated or at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms selected from the group consisting of N,O, and S, which heterocycles can be substituted by one or moresubstituents selected from the group consisting of halogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, where said heterocycles canoptionally be condensed to the said phenyl or the said group Hetar;wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in the saidsubstituents of the said phenyl or the said group Hetar, can besubstituted by one or more substituents selected from the groupconsisting of halogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy,and CF₃;

R⁵ is even more preferably a group Hetar which can be unsubstituted orcarry one or more substituents selected from the group consisting of. F;Cl; Br; C₁-C₃-alkyl; C₁-C₃-alkoxymethyl;2-amino-3,3,3-trifluoro-propyl-; CF₃; C₃-C₅-alkandiyl; phenyl;heteroaryl; benzyl; heteroaryl-methyl; OH; C₁-C₃-alkoxy; phenoxy;trifluoromethoxy; 2,2,2-trifluoroethoxy; (C₁-C₄-alkyl)COO;(C₁-C₃-alkyl)mercapto; phenylmercapto; (C₁-C₃-alkyl)sulfonyl;phenylsulfonyl; NH₂; (C₁-C₄-alkyl)amino; di(C₁-C₄-alkyl)amino;(C₁-C₃-alkyl)-CONH—; (C₁-C₃-alkyl)-SO₂NH—; (C₁-C₃-alkyl)-CO; phenyl-CO;—OCH₂O—; —OCF₂O; —CH₂CH₂O—; COO(C₁-C₄-alkyl); —CONH₂;—CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl)); CN; —SO₂NH₂;—SO₂NH(C₁-C₄-alkyl); —SO₂N(di(C₁-C₄-alkyl)); pyrrolidinyl; piperidinyl;morpholinyl; and thiomorpholinyl; wherein all heteroaryl, phenyl,heteroaryl-containing and phenyl-containing groups, which are optionallypresent in the said substituents of the said phenyl or the said groupHetar, can be substituted by one or more substituents selected from thegroup consisting of halogens, pseudohalogens, C₁-C₃-alkyl, OH,C₁-C₃-alkoxy, and CF₃;

R⁵ is most preferably selected from the group consisting of.benzo[1,3]dioxol-5-yl, 2,2-difluoro-benzo[1,3]dioxol-5-yl,2,3-dihydrobenzofuran-5-yl,1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-yl,1-(4-fluoro-phenyl)-3,5-dimethyl-1H-pyrazole-4-yl,1H-benzotriazole-5-yl, 1H-indole-4-yl, 1H-indole-6-yl,1-isopropyl-2-trifluoromethyl-1H-benzoimidazole-5-yl,1-methyl-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-yl,1-phenyl-5-trifluoromethyl-1H-pyrazole-4-yl,2-(2-hydroxy-pyridin-4-yl)-1H-benzoimidazole-5-yl,2-(4-cyano-phenyl)-1H-benzoimidazole-5-yl, 2,4-dimethyl-oxazole-5-yl,2,4-dimethyl-pyrimidine-5-yl, 2,4-dimethyl-thiazole-5-yl,2,5-dimethyl-1H-pyrrole-3-yl, 2,5-dimethyl-1-phenyl-1H-pyrrole-3-yl,2,5-dimethyl-1-pyridin-4-ylmethyl-1H-pyrrolyl,2,5-dimethyl-2H-pyrazole-3-yl, 2,6-dichloro-pyrid-3-yl,2,6-dimethoxy-pyrid-3-yl, 2,6-dimethyl-pyrid-3-yl,2-amino-4,6-dimethyl-pyrid-3-yl, 2-amino-6-chloro-pyrid-3-yl,2-amino-pyrid-3-yl, 2-chloro-6-methyl-pyrid-3-yl, 2-chloro-pyrid-4-yl,2-cyclopropyl-4-methyl-thiazole-5-yl,2-dimethylamino-4-methyl-thiazole-5-yl, 2-dimethylamino-pyrid-4-yl,2-ethyl-5-methyl-2H-pyrazole-3-yl, 2-hydroxy-6-methyl-pyrid-3-yl,2-methyl-1H-benzoimidazole-5-yl, 2-methyl-3H-benzoimidazole-5-yl,2-methyl-pyrid-3-yl, 2-methyl-6-trifluoromethyl-pyrid-3-yl,2-methyl-thiazole-5-yl, 2-morpholin-4-yl-pyridin-4-yl,2-morpholin-4-yl-pyrimidine-5-yl, 2-pyrrolidin-1-yl-pyridin-4-yl,3,5-dimethyl-1H-pyrazole-4-yl, 3-amino-5,6-dimethyl-pyrazine-2-yl,3-amino-5-methyl-pyrazine-2-yl, 3-amino-pyrazine-2-yl,3H-benzoimidazole-5-yl, 1H-benzoimidazole-5-yl, 3-methyl-isoxazole-4-yl,4,6-dimethylpyrid-3-yl, 4-amino-2-ethylsulfanyl-pyrimidine-5-yl,4-amino-2-methyl-pyrimidine-5-yl, 4-methyl-thiazole-5-yl, pyridine-2-yl,pyridine-3-yl, pyridine-4-yl, 5-thiophen-2-yl-pyrid-3-yl,2-methyl-4-trifluoromethyl-thiazol-5-yl,5,6,7,8-tetrahydro-quinoline-3-yl, 5-amino-1-phenyl-1H-pyrazole-4-yl,5-methyl-1-phenyl-1H-pyrazole-4-yl, 5-methyl-isoxazole-3-yl,5-methyl-pyrid-3-yl, 5-methyl-pyrazine-2-yl, 6-chloro-pyrid-3-yl,6-cyano-pyrid-3-yl, 6-dimethylamino-pyrid-3-yl, 6-ethynyl-pyrid-3-yl,6-methoxymethyl-pyrid-3-yl, 6-methoxypyrid-3-yl,6-methyl-2-methylamino-pyrid-3-yl, 6-methylamino-pyrazine-2-yl,6-methylpyrid-3-yl, 6-morpholin-4-yl-pyrid-3-yl,6-pyrrolidin-1-yl-pyrid-3-yl, imidazo[1,2a]pyridine-2-yl,6-trifluoromethyl-pyrid-3-yl, and pyrimidine-4-yl.

Heteroaryl is preferably a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one, two or three heteroatoms selected from thegroup consisting of N, O, and S; heteroaryl is most preferably selectedfrom the group consisting of: furyl, pyrrolyl, thienyl, thiazolyl,isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl,pyrazinyl, pyridyl, pyrimidinyl, benzoimidazolyl, benzothiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl,indolyl, benzofuranyl, benzothiophenyl, and indazolyl.

The group Hetar is preferably a 5 to 10-membered, aromatic, mono- orbicyclic heterocycle containing one, two or three heteroatoms selectedfrom the group consisting of N, O, and S; the group Hetar is mostpreferably selected from the group consisting of: furyl, pyrrolyl,thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl,imidazolyl, pyridazinyl, pyrazinyl, pyridyl, pyrimidinyl,benzoimidazolyl, benzothiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinoxalinyl, quinazolyl, indolyl, benzofaranyl,benzothiophenyl, and indazolyl.

Aryl is preferably phenyl.

m is preferably 0 or 2.

Compounds of the formula (I) in which some or all of the above-mentionedgroups have the preferred meanings, the more preferred meanings, theeven more preferred meanings, the most preferred meanings, or theparticularly preferred meanings defined above are also an object of thepresent invention.

In another embodiment of the present invention, the substituents R¹ toR⁵, A, B and C and the groups aryl and heteroaryl according to theformula (I) have the following meanings.

R¹ and R⁴ are independently from each other selected from the groupconsisting of: H; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents ofwhich are selected from the group consisting of F, OH, C₁-C₆-alkoxy,(C₁-C₆-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which areselected from the group consisting of halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which areselected from the group consisting of halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁹CO; CONR¹⁰,R¹¹, COOR¹²; CF₃;halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵; S(O)_(m)R¹⁶; SO₂NR¹⁷R¹⁸; andNO₂;

R² and R³ are independently of each other selected from the groupconsisting of: H; halogens; pseudohalogens; unsubstituted and at leastmonosubstituted C₁-C₆-alkyl, the substituents of which are selected fromthe group consisting of OH, phenyl, and heteroaryl; OH; C₁-C₆-alkoxy;phenoxy; S(O)_(m)R¹⁹; CF₃; CN; NO₂; (C₁-C₆-alkyl)amino;di(C₁-C₆-alkyl)amino; (C₁-C₆-alkyl)-CONH—; unsubstituted and at leastmonosubstituted phenyl-CONH and phenyl-SO₂—O—, the substituents of whichare selected from the group consisting of halogens, pseudohalogens, CH₃and methoxy; (C₁-C₆-alkyl)SO₂—O—, unsubstituted and at leastmonosubstituted (C₁-C₆-alkyl)CO, the substituents of which are selectedfrom the group consisting of F, di(C₁-C₃-alkyl)amino, pyrrolidinyl andpiperidinyl; and phenyl-CO, the phenyl part of which can be substitutedby one or more substituents from the group consisting of C₁-C₃-alkyl,halogens and methoxy;

A is CH₂, CHOH or CH—(C₁-C₃-alkyl);

B is CH₂ or CH—(C₁-C₃-alkyl);

C independently has the same meaning as B;

R⁵ is an aryl or a heteroaryl group which can be unsubstituted or carryone or more substituents selected from the group consisting of:halogens; pseudohalogens; C₁-C₁₀alkyl; C₃-C₅-alkandiyl; phenyl; phenylsubstituted C₁-C₄-alkyl; CF₃; OH; C₁-C₁₀-alkoxy; phenoxy; benzyloxy;CF₃O; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; (C₁-C₁₀-alkyl)amino;di(C₁C₁₀-alkyl)amino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₃-alkyl)-; (C₁-C₁₀alkyl)-CO; CF₃—CO; —OCH₂O—;—OCF₂O—; —OCH₂CH2O—; —CH₂CH2O—; phenylamino; phenyl-CO; COOR²¹;CONR²²R²³; SO₂NR²⁴R²⁵; and aromatic or aliphatic, mononuclear5-to-7-membered heterocycles containing 1 to 3 heteroatoms from thegroup consisting of N, O, and S which can be substituted by one or moresubstituents from the group consisting of halogens, C₁-C₃-alkyl,C₁-C₃-alkoxy and CF₃; wherein all phenyl groups and phenyl-containinggroups which may be present in the said substituents of the said aryl orheteroaryl groups can be substituted by one or more groups selected fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃; where withrespect to the group R₅ which can be an aryl or a heteroaryl group, aheteroaryl group is generally preferred over an aryl group, and saidheteroaryl group can be unsubstituted or substituted and carry at leastone of the substituents mentioned above in the definition relating toR⁵;

R⁶ is H, C₁-C₆-alkyl or benzyl;

R⁷ is selected from the group consisting of:

-   H; C₁-C₆-alkyl which can be phenyl-substituted; phenyl; indanyl; and    heteroaryl; and wherein each of the aforementioned aromatic groups    can be unsubstituted or carry one or more substituents from the    group consisting of halogens, pseudohalogens, C₁-C₃-alkyl,    C₁-C₃-alkoxy and CF₃;

R⁸ is H or C₁-C₆-alkyl;

R⁹ is C₁-C₆-alkyl which can be unsubstituted or carry one or moresubstituents from the group consisting of: F; di(C₁-C₃-alkyl)amino; andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are selected from the group consisting ofC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃;

R¹⁰ independently has the same meaning as R⁷;

R¹¹ independently has the same meaning as R⁸;

R¹² independently has the same meaning as R⁶;

R¹³ is selected from the group consisting of: H; C₁-C₆-alkyl; andunsubstituted and substituted phenyl, benzyl, heteroaryl, phenyl-CO, andheteroaryl-CO, the substituents of which are selected from the groupconsisting of halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, andCF₃, and wherein one or more of these substituents can be present;

R¹⁴ is H or C₁-C₆-alkyl;

R¹⁵ is selected from the group consisting of: H; C₁-C₆-alkyl; andsubstituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are selected from the group consisting ofhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, andwherein one or more of these substituents can be present;

R¹⁶ is selected from the group consisting of: —C₁-C₆-alkyl; CF₃; andsubstituted and unsubstituted phenyl and heteroaryl, the substituents ofwhich are selected from the group consisting of halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one ormore of these substitutents can be present;

R¹⁷ independently has the same meaning as R⁷;

R¹⁸ independently has the same meaning as R⁸;

R¹⁹ independently has the same meaning as R¹⁶;

R²⁰ independently has the same meaning as R¹⁶;

R²¹ independently has the same meaning as R⁶;

R²² independently has the same meaning as R⁷;

R²³ independently has the same meaning as R⁸;

R²⁴ independently has the same meaning as R⁷;

R²⁵ independently has the same meaning as R⁸;

heteroaryl is a 5 to 10-membered, mono- or bicyclic aromatic heterocyclecontaining one or more heteroatoms from the group consisting of N, O,and S;

aryl is phenyl, naphth-1-yl or naphth-2-yl;

m is 0, 1 or 2,

with the proviso that, in case R¹, R², R³ and R⁴ are hydrogen, R⁵ is notphenyl, 5-chloro-2-ethoxyphenyl, 5-chloro-2-methoxyphenyl,5-bromo-2-methoxyphenyl, 5-fluoro-2-methoxyphenyl,2-methoxy-5-methylphenyl, 3-alkylcarbonylamino-2-hydroxyphenyl orunsubstituted or substituted 4-oxoquinolinyl; and that, in case R⁵ isphenyl, A is not CHOH; and that, in case R⁵ is phenyl, R¹ is not hydroxyor methoxy; and that, in case R⁵ is phenyl, R² is not Br, hydroxy ormethoxy; and that, in case R⁵ is 3-pyridyl, R² is not hydroxy.

The compounds according to general formula (I) and their precursors canbe prepared according to methods published in the literature or,respectively, analogous methods. Appropriate methods have been publishedin, for example, Windaus; Chem. Ber. 57 (1924) 1735, Cannon, J. G. etal, J. Med. Chem. 17 (1974) 565, Itoh, K. et al., Chem. Pharm. Bull. 25(1977) 2917, Hillver et al, J. Med. Chem. 33 (1990) 1541, Copinga etal., J. Med. Chem. 36 (1993) 2891 and Trillat et al., Eur. J. Med. Chem.Chim. Ther. 33 (1998) 437. 1,2,3,4-Tetrahydronaphthyl amines preparedaccording to the disclosed methods can be dissolved in a solvent suchas, for example, dichloromethane, THF, toluene or dioxane and reacted inthe presence of base such as, for example, triethylamine, with anappropriate carboxylic acid derivative, for example, a carboxylic acidchloride. This reaction is preferably carried out at room temperature.

Alternatively, the compounds according to the general formula (I) areobtained by a coupling reaction of the respective1,2,3,4-tetrahydronaphthyl amines with an acid, which1,2,3,4-tetrahydronaphthyl amines and/or acid may be substituted and/orfunctionalized, in the presence of a base like, for example,diisopropylethylamine, and the use of an appropriate coupling reagentlike, for example, carbodiimides, HATU or TOTU. The thus obtained acyl1,2,3,4-tetrahydronaphthyl amines can then be functionalized, in orderto obtain further desired compounds according to the general formula(I). The reaction leading to the above-mentioned acyl1,2,3,4-tetrahydronaphthyl amines and the reactions used in thefunctionalization are known to the person skilled in the art.

All reactions for the synthesis of the compounds of the formula (I) areper se well-known to the skilled person and can be carried out understandard conditions according to or analogously to procedures describedin the literature, for example in Houben-Weyl, Methoden der OrganischenChemie (Methods of Organic Chemistry), Thieme-Verlag, Stuttgart, orOrganic Reactions, John Wiley & Sons, New York. Depending on thecircumstances of the individual case, in order to avoid side reactionsduring the synthesis of a compound of the formula (I), it can benecessary or advantageous to temporarily block functional groups byintroducing protective groups and to deprotect them in a later stage ofthe synthesis, or introduce functional groups in the form of precursorgroups which in a later reaction step are converted into the desiredfunctional groups. Such synthesis strategies and protective groups andprecursor groups which are suitable in an individual case are known tothe skilled person. If desired, the compounds of the formula (I) can bepurified by customary purification procedures, for example byrecrystallization or chromatography. The starting compounds for thepreparation of the compounds of the formula (I) are commerciallyavailable or can be prepared according to or analogously to literatureprocedures. The compounds obtained with the above-mentioned synthesismethods are a further object of the present invention.

Some of the compounds falling under formula (I) and their use aspharmaceutical agents are disclosed in the literature.

EP-A 0 253 257 discloses various acylated 1,2,3,4-tetrahydronaphthylamines falling under the general formula I and their use as precursorsfor the synthesis of pharmacologically active compounds.

EP-A 0 420 064 discloses the use of various compounds according to thegeneral formula I for therapeutic and diagnostic purposes like insomniaand psychic diseases. The treatment of cardiovascular diseases is notdisclosed. Compounds disclosed by EP-A 0 420 064 include 2-amidotetralinderivatives of the general formula (II).

In the above formula, X₁-X₅ have the following meaning:

-   X₁ is hydrogen, halogen, amino, amido, a C₁₋₄ alkyl, alkoxyl, or    alkoxylaryl;-   X₂ is hydrogen, hydroxyl, halogen, amino, amido, aryl, mono- or    di-C₁₋₄ alkylamino, C₁₋₄ alkylaryl, or alkoxylaryl, or C₁₋₄ alkyl,    alkenyl, alkynl, alkoxyl;-   X₃ is hydrogen, aryl, C₁₋₄ alkylaryl, or C₁₋₄ alkyl, alkenyl, or    alkynl;-   X₄ is aryl, C₁₋₄ alkylaryl, or C₁₋₄ alkyl, haloalkyl, or cycloalkyl;-   X₅ is hydrogen, hydroxyl, halogen, oxo, aryl, C₁₋₄ alkylaryl, or    C₁₋₄ alkyl;-   wherein aryl substitutents of X₂, X₃, X₄ and X₅ may optionally be    halogen, hydroxyl, amino, mono- or di-C₁₋₄ alkylamino, or C₁₋₄ alkyl    or alkoxyl substituted, provided that when X₁ is methoxy, and X₂,    X₃, and X₅ are hydrogen, X₄ is not methyl.    Compounds explicitly disclosed by EP-A 0 420 064 are not an object    of the present invention.

WO 00/51970 discloses compounds according to the general formula (III)and their use for the potentiation of cholinergic activity.

In the above formula:

-   Z¹ and Z² are each aryl or ar(lower)alkyl, or are taken together to    form lower alkylene or lower alkenylene, each of which may be    substituted with aryl or may be condensed with a cyclic hydrocarbon    optionally substituted with lower alkyl, lower alkoxy, aryl, aryloxy    or halogen,-   Z³ is lower alkyl, lower alkoxy, aryl, arylamino or aryloxy, each of    which may be substituted with lower alkoxy or halogen, pyridyl, or    pyridylamino,-   X is CH or N,-   Y is a single bond or —NH—, and-   Q is

Referring to the definition of Z¹ and Z² in formula (III), it is statedthat preferred lower alkylenes are tetramethylene or pentamethylene,preferred lower alkenylenes are butenylene, pentenylene ormethylpentenylene, a preferred cyclic hydrocarbon is benzene and apreferred aryl is phenyl.

Furthermore, it is stated that, among other preferred compoundsaccording to the general formula (III) are those having lower alkenylenewhich may be substituted with aryl or may be condensed with benzeneoptionally substituted with lower alkoxy for Z¹ and Z² to be takentogether to form, aryl or arylamino, each of which may be substitutedwith halogen, pyridyl, or pyridylamino for Z³, CH or N for X, a singlebond or —NH— for Y, and

for Q.

More preferred compounds according to the general formula (III) arethose having Z¹ and Z² taken together to form methylpentenylene,butenylene condensed with benzene or pentenylene which may be condensedwith benzene optionally substituted with lower alkoxy.

As examples, there are provided2-(4-fluorobenzoylamino)-1,2,3,4,-tetrahydronaphthalene,2-(pyridin-4-ylcarbonylamino)-1,2,3,4-tetrahydronaphthalene,(R)-4-fluoro-N-(1,2,3,4tetrahydronaphthalen-2-yl)-benzamide,(S)-4-fluoro-N-(1,2,3,4-tetrahydronaphthalen-2-yl)-benzamide,4-fluoro-N-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-benzamide and4-fluoro-N-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-benzamide.

Compounds explicitly disclosed by WO 00/51970 are not an object of thepresent invention.

The object of the present invention is furthermore attained by the useof acylated 1,2,3,4-tetrahydronaphthyl amines according to the generalformula (I) in any of their stereoisomeric forms or mixtures thereof inany ratio or the pharmaceutically acceptable salts thereof for themanufacture of a medicament for the stimulation of the expression ofendothelial NO-synthase.

In the above formula,

-   R¹ and R⁴ are independently from each other selected from the group    consisting of:-   H; unsubstituted and at least monosubstituted C₁-C₁₀-alkyl,    C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents of which are    selected from the group consisting of F, OH, C₁-C₈-alkoxy,    (C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, and unsubstituted and at    least monosubstituted phenyl and heteroaryl, the substituents of    which are selected from the group consisting of halogens,    pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and    at least monosubstituted phenyl and heteroaryl, the substituents of    which are selected from the group consisting of halogens,    pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁹CO; CONR¹⁰R¹¹;    COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵; S(O)_(m)R¹⁶;    SO₂NR¹⁷R¹⁸; and NO₂;

R² and R³ are independently from each other selected from the groupconsisting of:

-   H; halogens; pseudohalogens; unsubstituted and at least    monosubstituted C₁-C₁₀-alkyl the substituents of which are selected    from the group consisting of OH, phenyl, and heteroaryl; OH;    C₁-C₁₀-alkoxy; phenoxy; S(O)_(m)R¹⁹; CF₃; CN; NO₂;    (C₁-C₁₀-alkyl)amino; di(C₁-C₁₀-alkyl)amino; (C₁-C₆-alkyl)-CONH—;    unsubstituted and at least monosubstituted phenyl-CONH— and    phenyl-SO₂—O—, the substituents of which are selected from the group    consisting of halogens, pseudohalogens, CH₃ and methoxy;    (C₁-C₆-alkyl)SO₂—O—; unsubstituted and at least monosubstituted    (C₁-C₆-alkyl)CO, the substituents of which are selected from the    group consisting of F, di(C₁-C₃-alkyl)amino, pyrrolidinyl and    piperidinyl; and phenyl-CO, the phenyl part of which can be    substituted by one or more substituents from the group consisting of    C₁-C₃-alkyl, halogens and methoxy;

A is selected from the group consisting of CH₂, CHOH andCH—(C₁-C₃-alkyl);

B is selected from the group consisting of CH₂ and CH—(C₁-C₃-alkyl);

C independently has the same meaning as B;

R⁵ is a group Ar or a group Hetar both of which can be unsubstituted orcarry one or more substituents selected from the group consisting of.halogens; pseudohalogens; NH₂; unsubstituted and at leastmonosubstituted C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl,C₁-C₁₀-alkoxy, (C₁-C₁₀-alkyl)amino, di(C₁-C₁₀-alkyl)amino, thesubstituents of which are selected from the group consisting of F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino,and di(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl; aryl- orheteroaryl-substituted C₁-C₄-alkyl; CF₃; NO₂; OH; phenoxy; benzyloxy;(C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH; phenylamino; benzylamino;(C₁-C₁₀-alkyl)-CONH—; (C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR²⁴R²⁵; R²⁶SO₂NH—; R²⁷SO₂N(C₁-C₆-alkyl)-; andsaturated or at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms selected from thegroup consisting of N, O and S, which heterocycles can be substituted byone or more substituents selected from the group consisting of halogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, where said heterocycles canoptionally be condensed to the said group Ar or the said group Hetar;wherein all aryl, heteroaryl, phenyl, aryl-containing,heteroaryl-containing and phenyl-containing groups, which are optionallypresent in the said substituents of the said group Ar or the said groupHetar, can be substituted by one or more substituents selected from thegroup consisting of halogens, pseudohalogens, C₁-C₃-alkyl, OH,C₁-C₃-alkoxy, and CF₃;

R⁶ is selected from the group consisting of:

-   H; C₁-C₁₀-alkyl, which can be substituted by one or more    substituents selected from the group consisting of F, C₁-C₈-alkoxy,    and di(C₁-C₈-alkyl)amino; aryl-(C₁-C₄-alkyl) and    heteroaryl-(C₁-C₄-alkyl), which can be substituted by one or more    substituents selected from the group consisting of halogens,    C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino;

R⁷ is selected from the group consisting of:

-   H; C₁-C₁₀-alkyl which can be substituted by one or more substituents    selected from the group consisting of F, C₁-C₈-alkoxy,    di(C₁-C₈-alkyl)amino and phenyl; phenyl; indanyl;

and heteroaryl; and wherein each of the aforementioned aromatic groupscan be unsubstituted or carry one or more substituents from the groupconsisting of halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy andCF₃;

R⁸ is H or C₁-C₁₀-alkyl;

R⁹ is selected from the group consisting of: C₁-C₁₀-alkyl which can beunsubstituted or carry one or more substituents from the groupconsisting of: F, (C₁-C₄)-alkoxy, di(C₁-C₃-alkyl)amino; andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are selected from the group consisting ofC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃;

R¹⁰ independently has the same meaning as R⁷;

R¹¹ independently has the same meaning as R⁸;

R¹² independently has the same meaning as R⁶;

R¹³ is selected from the group consisting of: H; C₁-C₆-alkyl;unsubstituted and substituted phenyl, benzyl, heteroaryl,(C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, the substituents ofwhich are selected from the group consisting of halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one ormore of these substituents can be present;

R¹⁴ independently has the same meaning as R¹³;

R¹⁵ is selected from the group consisting of: H; C₁-C₁₀-alkyl;(C₁-C₃-alkoxy)-C₁-C₃-alkyl; and substituted and unsubstituted benzyl,phenyl and heteroaryl, the substituents of which are selected from thegroup consisting of halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy,and CF₃, and wherein one or more of these substituents can be present;

R¹⁶ is selected from the group consisting of: C₁-C₁₀-alkyl which can besubstituted by one or more substituents selected from the groupconsisting of F, OH, C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto,(C₁-C₈-alkyl)amino and di(C₁-C₈-alkyl)amino; CF₃; and substituted andunsubstituted phenyl and heteroaryl, the substituents of which areselected from the group consisting of halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one or more of thesesubstitutents can be present;

R¹⁷ independently has the same meaning as R⁷;

R¹⁸ independently has the same meaning as R⁸;

R¹⁹ independently has the same meaning as R¹⁶;

R²⁰ independently has the same meaning as R¹⁶;

R²¹ independently has the same meaning as R⁶;

R²² independently has the same meaning as R⁷;

R²³ independently has the same meaning as R⁸;

R²⁴ independently has the same meaning as R⁷;

R²⁵ independently has the same meaning as R⁸;

R²⁶ independently has the same meaning as R¹⁶;

R²⁷ independently has the same meaning as R¹⁶;

heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms selected from the groupconsisting of N, O, and S;

the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms selected from the groupconsisting of N, O, and S;

aryl is phenyl, naphth-1-yl or naphth-2-yl;

the group Ar is phenyl, naphth-1-yl or naphth-2-yl; and

m is 0, 1 or 2.

Furthermore, with respect to the definitions given above in the contextof the compounds according to the general formula (I) for use in themanufacture of a medicament, the same explanations as laid out above inthe context with the compounds as such apply.

In preferred embodiments, the object of the present invention isattained by the use of acylated 1,2,3,4-tetrahydronaphthyl aminesaccording to the general formula (I) in any of their stereoisomericforms or mixtures thereof in any ratio or the pharmaceuticallyacceptable salts thereof for the manufacture of a medicament for thestimulation of the expression of endothelial NO-synthase, wherein thesubstituents R¹ to R⁵, A, B and C and the groups aryl and heteroaryl ofthe formula (I) independently from each other have the followingmeanings. Hence, one or more of the substituents R¹ to R⁵ and A, B and Ccan have the preferred, the more preferred, the even more preferred, themost preferred or particularly preferred meanings specified below.

R¹ is preferably selected from the group consisting of: H; C₁-C₄-alkyl;C₁-C₄-alkoxy; CF₃; halogens; pseudohalogens; (C₁-C₄-alkyl)-S(O)_(m)—;and unsubstituted and at least monosubstituted phenyl and heteroaryl,the substituents of which are selected from the group consisting ofhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, whereheteroaryl is selected from the group consisting of 5- and 6-memberedheterocycles containing one or more heteroatoms selected from the groupconsisting of N, O, and S; R¹ is more preferably H, halogen orC₁-C₄-alkyl.

R² is preferably selected from the group consisting of: H; halogens;pseudohalogens; and C₁-C₃-alkyl; R₂ is more preferably H.

R³ is preferably selected from the group consisting of: H; halogens;pseudohalogens; and C₁-C₃-alkyl; R³ is more preferably H.

R⁴ is preferably selected from the group consisting of: H; C₁-C₄-alkyl;C₁-C₄-alkoxy; CF₃; halogens; pseudohalogens; (C₁-C₄-alkyl)-S(O)_(m)—;and unsubstituted and at least monosubstituted phenyl and heteroaryl,the substituents of which are selected from the group consisting ofhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, whereheteroaryl is selected from the group consisting of 5- and 6-memberedheterocycles containing one or more heteroatoms selected from the groupconsisting of N, O, and S; R⁴ is more preferably H, halogen orC₁-C₄-alkyl; R⁴ is most preferably H.

R¹ to R⁴ are in particular each H.

A is preferably selected from the group consisting of CH₂ and CHOH; A isin particular CH₂.

B and C are preferably independently from each other selected from thegroup consisting of CH₂ and CH—CH₃; more preferably B is a CH₂ unitwhile C is CH₂ or CH—CH₃; most preferably B and C are CH₂.

R⁵ is preferably selected from the group consisting of: a group Ar or agroup Hetar both of which can be unsubstituted or carry one or moresubstituents selected from the group consisting of: halogens; CN; NH₂;unsubstituted and at least monosubstituted C₁-C₈-alkyl, C₂-C₈-alkenyl,C₂-C₈-alkynyl, C₁-C₈-alkoxy, (C₁-C₈-alkyl)amino, di(C₁-C₈-alkyl)amino,the substituents of which are selected from the group consisting of F,C₁-C₆-alkoxy, phenoxy, (C₁-C₆-alkyl)mercapto, NH₂, (C₁-C₆-alkyl)amino,and di(C₁-C₆-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl; phenyl-or heteroaryl-substituted C₁-C₂-alkyl; CF₃; OH; phenoxy; benzyloxy;(C₁-C₆-alkyl)COO; S(O)_(m)(C₁-C₆)-alkyl; S(O)_(m)-phenyl;S(O)_(m)-heteroaryl; SH; phenylamino; benzylamino; (C₁-C₆-alkyl)-CONH—;(C₁-C₆-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—; phenyl-CON(C₁-C₄-alkyl)-;heteroaryl-CONH—; heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₆-alkyl)-CO;phenyl-CO; heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—;—CH₂CH₂O—; COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₆-alkyl);—CON(di(C₁-C₆-alkyl)); CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₆-alkyl);—SO₂NH(phenyl); —SO₂N(di(C₁-C₆-alkyl)); (C₁-C₆-alkyl)SO₂NH—;(C₁-C₆-alkyl)SO₂N(C₁-C₆-alkyl)-; phenyl-SO₂NH—;phenyl-SO₂N(C₁-C₆-alkyl)-; heteroaryl-SO₂NH—;heteroaryl-SO₂N(C₁-C₆-alkyl)-; and saturated or at least monounsaturatedaliphatic, mononuclear 5- to 7-membered heterocycles containing 1 to 3heteroatoms selected from the group consisting of N, O, and S, whichheterocycles can be substituted by one or more substituents selectedfrom the group consisting of halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH,oxo and CF₃, where said heterocycles can optionally be condensed to thesaid group Ar or the said group Hetar; wherein all heteroaryl, phenyl,heteroaryl-containing and phenyl-containing groups, which are optionallypresent in the said substituents of the said group Ar or the said groupHetar, can be substituted by one or more substituents selected from thegroup consisting of halogens, pseudohalogens, C₁-C₃-alkyl, OH,C₁-C₃-alkoxy, and CF₃;

R⁵ is more preferably selected from the group consisting of: phenyl or agroup Hetar both of which can be unsubstituted or carry one or moresubstituents selected from the group consisting of. halogens; CN; NH₂;unsubstituted and at least monosubstituted C₁-C₆-alkyl, C₂-C₆-alkenyl,C₂-C₆-alkynyl, C₁-C₃-alkoxy, (C₁-C₄-alkyl)amino, di(C₁-C₄-alkyl)amino,the substituents of which are selected from the group consisting of F,C₁-C₃-alkoxy, (C₁-C₃-alkyl)mercapto, and NH₂; C₃-C₅-alkandiyl; phenyl;heteroaryl; phenyl- or heteroaryl-substituted C₁-C₂-alkyl; CF₃; OH;(C₁-C₄-alkyl)COO; S(O)(C₁-C₄)-alkyl; (C₁-C₄-alkyl)-CONH—;(C₁-C₄-alkyl)-CON(C₁-C₄-alkyl)-; (C₁-C₄-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O0—; —CH₂CH₂O—;COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl));CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂NH(phenyl);—SO₂N(di(C₁-C₄-alkyl)); (C₁-C₄-alkyl)SO₂NH—;(C₁-C₄-alkyl)SO₂N(C₁-C₄-alkyl)-; and saturated or at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms selected from the group consisting of N,O, and S, which heterocycles can be substituted by one or moresubstituents selected from the group consisting of halogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, where said heterocycles canoptionally be condensed to the said phenyl or the said group Hetar;wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in the saidsubstituents of the said phenyl or the said group Hetar, can besubstituted by one or more substituents selected from the groupconsisting of halogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy,and CF₃;

R⁵ is even more preferably selected from the group consisting of: phenylor a group Hetar both of which can be unsubstituted or carry one or moresubstituents selected from the group consisting of: F; Cl; Br;C₁-C₃-alkyl; Cl—C₃-alkoxymethyl; 2-amino-3,3,3-trifluoropropyl; CF₃;C₃-C₅-alkandiyl; phenyl; heteroaryl; benzyl; heteroaryl-methyl; OH;C₁-C₃-alkoxy; phenoxy; trifluoromethoxy; 2,2,2-trifluoroethoxy;(C₁-C₄-alkyl)COO; (C₁-C₃-alkyl)mercapto; phenylmercapto;(C₁-C₃-alkyl)sulfonyl; phenylsulfonyl; NH₂; (C₁-C₄-alkyl)amino;di(C₁-C₄-alkyl)amino; (C₁-C₃-alkyl)-CONH—; (C₁-C₃-alkyl)-SO₂NH—;(C₁-C₃-alkyl)-CO; phenyl-CO; —OCH₂O—; —OCF₂O—; —CH₂CH₂O—;COO(C₁-C₄-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl)); CN;—SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂N(di(C₁-C₄-alkyl)); pyrrolidinyl;piperidinyl; morpholinyl; and thiomorpholinyl; wherein all heteroaryl,phenyl, heteroaryl-containing and phenyl-containing groups, which areoptionally present in the said substituents of the said phenyl or thesaid group Hetar, can be substituted by one or more substituentsselected from the group consisting of halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;

R⁵ is most preferably selected from the group consisting of:4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-(C₁-C₃-alkoxy)-phenyl,4-trifluoromethoxyphenyl, 2-bromo-4-fluorophenyl,2-chloro-4-fluorophenyl, 3,4-dimethylphenyl, 2,4-dimethylphenyl,4-chloro-2-methylphenyl, 2-hydroxy-4-methylphenyl,2-hydroxy-4-ethoxyphenyl, 2-methoxy-4-methylphenyl, 4-phenoxyphenyl,3-fluoro-4-methylphenyl, benzo[1,3]dioxol-5-yl,2,2-difluoro-benzo[1,3]dioxol-5-yl, 2,3-dihydrobenzofuran-5-yl,1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-yl,1-(4-fluoro-phenyl)-3,5-dimethyl-1H-pyrazole-4-yl,1H-benzotriazole-5-yl, 1H-indole-4-yl, 1H-indole-6-yl,1-isopropyl-2-trifluoromethyl-1H-benzoimidazole-5-yl,1-methyl-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-yl,1-phenyl-5-trifluoromethyl-1H-pyrazole-4-yl,2-(2-hydroxy-pyridin-4-yl)-1H-benzoimidazole-5-yl,2-(4-cyano-phenyl)-1H-benzoimidazole-5-yl, 2,4-dimethyl-oxazole-5-yl,2,4-dimethyl pyrimidine-5-yl, 2,4-dimethyl-thiazole-5-yl,2,5-dimethyl-1H-pyrrole-3-yl, 2,5-dimethyl-1-phenyl-1H-pyrrole-3-yl,2,5-dimethyl-1pyridin-4-ylmethyl-1H-pyrrolyl,2,5-dimethyl-2H-pyrazole-3-yl, 2,6-dichloro-pyrid-3-yl,2,6-dimethoxy-pyrid-3-yl, 2,6-dimethyl-pyrid-3-yl,2-amino-4,6-dimethyl-pyrid-3-yl, 2-amino-6-chloro-pyrid-3-yl,2-amino-pyrid-3-yl, 2-chloro-6-methyl-pyrid-3-yl, 2-chloro-pyrid-4-yl,2-cyclopropyl-4-methyl-thiazole-5-yl,2-dimethylamino-4-methyl-thiazole-5-yl, 2-dimethylamino-pyrid-4-yl,2-ethyl-5-methyl-2H-pyrazole-3-yl, 2-hydroxy-6-methyl-pyrid-3-yl,2-methyl-IH-benzoimidazole-5-yl, 2-methyl-3H-benzoimidazole-5-yl,2-methyl-pyrid-3-yl, 2-methyl-6-trifluoromethyl-pyrid-3-yl,2-methyl-thiazole-5-yl, 2-morpholin-4-yl-pyridin-4-yl,2-morpholin-4-yl-pyrimidine-5-yl, 2-pyrrolidin-1-yl-pyridin-4-yl,3,5-dimethyl-1H-pyrazole-4-yl, 3-amino-5,6-dimethyl-pyrazine-2-yl,3-amino-5-methyl-pyrazine-2-yl, 3-amino-pyrazine-2-yl,3-dimethylamino-4-methyl-phenyl, 3-dimethylamino-phenyl,3H-benzoimidazole-5-yl, 1H-benzoimidazole-5-yl,3-methanesulfonylainino-2-methyl-phenyl, 3-methanesulfonylamino-phenyl,3-methyl-isoxazole-4-yl, 3-morpholin-4-yl-phenyl,3-piperidin-1-yl-phenyl, 3-pyrrolidin-1-yl-phenyl,4-(2,2,2-trifluoro-ethoxy)-phenyl, 4,6-dimethyl-pyrid-3-yl,4-amino-2-ethylsulfanyl-pyrimidine-5-yl,4-amino-2-methyl-pyrimidine-5-yl,4-chloro-3-methanesulfonylamino-phenyl, 4-chloro-3-sulfamoyl-phenyl,4-methyl-3-methylamino-phenyl, 4-methyl-thiazole-5-yl, pyridine-2-yl,pyridine-3-yl, pyridine-4-yl, 5-thiophen-2-yl-pyrid-3-yl,2-methyl-4-trifluoromethyl-thiazol-5-yl,5,6,7,8-tetrahydro-quinoline-3-yl, 5-amino-1-phenyl-1H-pyrazole-4-yl,5-methanesulfonyl-2-methyl-phenyl, 5-methyl-1-phenyl-1H-pyrazole-4-yl,5-methyl-isoxazole-3-yl, 5-methyl-pyrid-3-yl, 5-methyl-pyrazine-2-yl,6-chloro-pyrid-3-yl, 6-cyano-pyrid-3-yl, 6-dimethylamino-pyrid-3-yl,6-ethynyl-pyrid-3-yl, 6-methoxymethyl-pyrid-3-yl, 6-methoxy-pyrid-3-yl,6-methyl-2-methylamino-pyrid-3-yl, 6-methylamino-pyrazine-2-yl,6-methyl-pyrid-3-yl, 6-morpholin-4-yl-pyrid-3-yl,6-pyrrolidin-1-yl-pyrid-3-yl, imidazo[1,2-a]pyridine-2-yl,6-trifluoromethyl-pyrid-3-yl, and pyrimidine-4-yl.

Heteroaryl is preferably a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one, two or three heteroatoms selected from thegroup consisting of N, O, and S; heteroaryl is most preferably selectedfrom the group consisting of: furyl, pyrrolyl, thienyl, thiazolyl,isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl,pyrazinyl, pyridyl, pyrimidinyl, benzoimidazolyl, benzthiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl,indolyl, benzofaranyl, benzothiophenyl, and indazolyl.

The group Hetar is preferably a 5 to 10-membered, aromatic, mono- orbicyclic heterocycle containing one, two or three heteroatoms selectedfrom the group consisting of N, O and S; the group Hetar is mostpreferably selected from the group consisting of. furyl, pyrrolyl,thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl,imidazolyl, pyridazinyl, pyrazinyl, pyridyl, pyrimidinyl,benzoimidazolyl, benzothiazolyl, benzoxazolyl, quinolinyl,isoquinolinyl, quinoxalinyl, quinazolyl, indolyl, benzofuranyl,benzothiophenyl, and indazolyl.

Aryl is preferably phenyl.

m is preferably 0 or 2.

Compounds of the formula (I) used for the manufacture of a medicamentfor the stimulation of the expression of endothelial NO-synthase, inwhich one or more, including all of the above-mentioned groups have thepreferred meanings, the more preferred meanings, the even more preferredmeanings, the most preferred meanings or the particularly preferredmeanings defined above are also an object of the present invention.

In a further embodiment, the object of the present invention is attainedby compounds of the formula (I) in any of their stereoisomeric forms ormixtures thereof in any ratio or the pharmaceutically acceptable saltsthereof used for the manufacture of a medicament for the stimulation ofthe expression of endothelial NO-synthase wherein the substituents R¹ toR⁵, A, B and C and the groups aryl and heteroaryl have the followingmeanings.

R¹ and R⁴ are independently from each other selected from the groupconsisting of:

-   H; unsubstituted and at least monosubstituted C₁-C₁₀-alkyl,    C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents of which are    selected from the group consisting of F, OH, C₁-C₆-alkoxy,    (C₁-C₆-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, unsubstituted and at    least monosubstituted phenyl and heteroaryl, the substituents of    which are selected from the group consisting of halogens,    pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and    at least monosubstituted phenyl and heteroaryl, the substituents of    which are selected from the group consisting of halogens,    pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁹CO; CONR¹⁰R¹¹;    COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴OR¹⁵; S(O)_(m)R¹⁶;    SO₂NR¹⁷R¹⁸; and NO₂;

R² and R³ are independently from each other selected from the groupconsisting of:

-   H; halogens; pseudohalogens; unsubstituted and at least    monosubstituted C₁-C₆-alkyl. the substituents of which are selected    from the group consisting of OH, phenyl, and heteroaryl; OH;    C₁-C₆-alkoxy; phenoxy; S(O)_(m)R¹⁹; CF₃; CN; NO₂;    (C₁-C₆-alkyl)amino; di(C₁-C₆-alkyl)amino; (C₁-C₆-alkyl)-CONH—;    unsubstituted and at least monosubstituted phenyl-CONH and    phenyl-SO₂—O—, the substituents of which are selected from the group    consisting of halogens, pseudohalogens, CH₃ and methoxy;    (C₁-C₆-alkyl)SO₂—O—; unsubstituted and at least monosubstituted    (C₁-C₆-alkyl)CO, the substituents of which are selected from the    group consisting of F, di(C₁-C₃-alkyl)amino, pyrrolidinyl and    piperidinyl; and phenyl-CO, the phenyl part of which can be    substituted by one or more substituents from the group consisting of    C₁-C₃-alkyl, halogens and methoxy;

A is CH₂, CHOH or CH—(C₁-C₃-alkyl);

B is CH₂ or CH—(C₁-C₃-alkyl);

C independently has the same meaning as B;

R⁵ is an aryl or a heteroaryl group which can be unsubstituted or carryone or more substituents selected from the group consisting of:halogens; pseudohalogens; C₁-C₁₀-alkyl; C₃-C₅-alkandiyl; phenyl; phenylsubstituted C₁-C₄-alkyl; CF₃; OH; C₁-C₁₀-alkoxy; phenoxy; benzyloxy;CF₃O; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; (C₁-C₁₀-alkyl)amino;di(C₁-C₁₀-alkyl)amino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₃-alkyl)-; (C₁-C₁₀-alkyl)-CO; CF₃—CO; —OCH₂O—;—OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; phenylamino; phenyl-CO; COOR²¹;CONR²²R²³; SO₂NR²⁴R²⁵; and aromatic or aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms from the groupconsisting of N, O, and S which can be substituted by one ore moresubstituents from the group consisting of halogens, C₁-C₃-alkyl,C₁-C₃-alkoxy and CF₃; wherein all phenyl groups and phenyl-containinggroups which may be present in the said substituents of the said aryl orheteroaryl groups can be substituted by one or more groups selected fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃; where withrespect to the group R⁵ which can be an aryl or a heteroaryl. group, aheteroaryl group is generally preferred over an aryl group, and saidheteroaryl group can be unsubstituted or substituted and carry at leastone of the substituents mentioned above in the definition relating toR⁵;

R⁶ is H, C₁-C₆-alkyl or benzyl;

R⁷ is selected from the group consisting of:

-   H; C₁-C₆-alkyl which can be phenyl-substituted; phenyl; indanyl; and    heteroaryl; and wherein each of the aforementioned aromatic groups    can be unsubstituted or carry one or more substituents from the    group consisting of halogens, pseudohalogens, C₁-C₃-alkyl,    C₁-C₃-alkoxy and CF₃;

R⁸ is H or C₁-C₆-alkyl;

R⁹ is C₁-C₆-alkyl which can be unsubstituted or carry one or moresubstituents from the group consisting of: F; di(C₁-C₃-alkyl)amino; andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are selected from the group consisting ofC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃;

R¹⁰ independently has the same meaning as R⁷;

R¹¹ independently has the same meaning as R⁸;

R¹² independently has the same meaning as R⁶;

R¹³ is selected from the group consisting of: H; C₁-C₆-alkyl; andunsubstituted and substituted phenyl, benzyl, heteroaryl, phenyl-CO, andheteroaryl-CO, the substituents of which are selected from the groupconsisting of halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, andCF₃, and wherein one or more of these substituents can be present;

R¹⁴ is H or C₁-C₆-alkyl;

R¹⁵ is selected from the group consisting of: H; C₁-C₆-alkyl; andsubstituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are selected from the group consisting ofhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, andwherein one or more of these substituents can be present;

R¹⁶ is selected from the group consisting of: C₁-C₆-alkyl; CF₃; andsubstituted and unsubstituted phenyl and heteroaryl, the substituents ofwhich are selected from the group consisting of halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one ormore of these substitutents can be present;

R¹⁷ independently has the same meaning as R⁷;

R¹⁸ independently has the same meaning as R⁸;

R¹⁹ independently has the same meaning as R¹⁶;

R²⁰ independently has the same meaning as R¹⁶;

R²¹ independently has the same meaning as R⁶;

R²² independently has the same meaning as R⁷;

R²³ independently has the same meaning as R⁸;

R²⁴ independently has the same meaning as R⁷;

R²⁵ independently has the same meaning as R⁸;

heteroaryl is a 5 to 10-membered, mono- or bicyclic aromatic heterocyclecontaining one or more heteroatoms from the group consisting of N, O,and S;

aryl is phenyl, naphth-1-yl or naphth-2-yl;

m is 0, 1 or 2.

The compounds according to the general formula (I) can be used toupregulate the expression of the endothelial NO synthase and are helpfulpharmaceutical compounds for the treatment of various diseases. In thecontext of the present invention, treatment includes the therapy as wellas the prophylaxis of the respective diseases.

Examples of diseases which can be treated with the compounds accordingto the present invention include cardiovascular diseases like stable andunstable angina pectoris, coronary heart disease, Prinzmetal angina(spasm), acute coronary syndrome, heart failure, myocardial infarction,stroke, thrombosis, peripheral artery occlusive disease (PAOD),endothelial dysfunction, atherosclerosis, restenosis, endothelial damageafter PTCA, hypertension including essential hypertension, pulmonaryhypertension, and secondary hypertension (renovascular hypertension,chronic glomerulonephritis), erectile dysfunction, ventriculararrhythmia, and the lowering of cardiovascular risk of postmenopausalwomen or after intake of contraceptives.

Compounds of the formula (I) can additionally be used in the therapy andprophylaxis of diabetes and diabetes complications (nephropathy,retinopathy), angiogenesis, asthma bronchiale, chronic renal failure,cirrhosis of the liver, osteoporosis, restricted memory performance or arestricted ability to learn.

Preferred indications are stable angina pectoris, coronary heartdisease, hypertension, endothelial dysfunction, atherosclerosis anddiabetes complications.

The compounds according to the formula (I) can also be used incombination with other pharmaceutically active compounds, preferablycompounds which are able to enhance the effect of the compoundsaccording to the general formula (I). Examples of such compoundsinclude: statins; ACE-inhibitors; AT1-antagonists;argininase-inhibitors; PDE V-inhibitors; Ca-antagonists; alpha-blockers;beta-blockers; metimazol and analogous compounds; arginine;tetrahydrobiopterin; vitamins, in particular vitamin C and vitamin B6;and niacin.

The compounds of the formula (I) and their pharmaceutically acceptablesalts, optionally in combination with other pharmaceutically activecompounds, can be administered to animals, preferably to mammals, and inparticular to humans, as pharmaceuticals by themselves, in mixtures withone another or in the form of pharmaceutical preparations. Furthersubjects of the present invention therefore also are the compounds ofthe formula (I) and their pharmaceutically acceptable salts for use aspharmaceuticals, their use as transcription stimulating agent forendothelial NO synthase and in particular their use in the therapy andprophylaxis of the above-mentioned syndromes as well as their use forpreparing medicaments for these purposes. Furthermore, subjects of thepresent invention are pharmaceutical preparations (or pharmaceuticalcompositions) which comprise an effective dose of at least one compoundof the formula (I) and/or a pharmaceutically acceptable salt thereof anda pharmaceutically acceptable carrier, i.e. one or more pharmaceuticallyacceptable carrier substances and/or additives.

The pharmaceuticals according to the invention can be administeredorally, for example in the form of pills, tablets, lacquered tablets,sugar-coated tablets, granules, hard and soft gelatin capsules, aqueous,alcoholic or oily solutions, syrups, emulsions or suspensions, orrectally, for example in the form of suppositories. Administration canalso be carried out parenterally, for example subcutaneously,intramuscularly or intravenously in the form of solutions for injectionor infusion. Other suitable administration forms are, for example,percutaneous or topical administration, for example in the form ofointments, tinctures, sprays or transdermal therapeutic systems, or theinhalative administration in the form of nasal sprays or aerosolmixtures, or, for example, microcapsules, implants or rods. Thepreferred administration form depends, for example, on the disease to betreated and on its severity.

The amount of compounds of the formula (I) and/or its pharmaceuticallyacceptable salts in the pharmaceutical preparations normally ranges from0.2 to 800 mg, preferably from 0.5 to 500 mg, in particular from 1 to200 mg, per dose, but depending on the type of the pharmaceuticalpreparation it may also be higher. The pharmaceutical preparationsusually comprise 0.5 to 90 percent by weight of the compounds of theformula (I) and/or their pharmaceutically acceptable salts. Thepreparation of the pharmaceutical preparations can be carried out in amanner known per se. To this end, one or more compounds of the formula(I) and/or their pharmaceutically acceptable salts, together with one ormore solid or liquid pharmaceutical carrier substances and/or additives(or auxiliary substances) and, if desired, in combination with otherpharmaceutically active compounds having therapeutic or prophylacticaction, are brought into a suitable administration form or dosage formwhich can then be used as a pharmaceutical in human or veterinarymedicine.

For the production of pills, tablets, sugar-coated tablets and hardgelatin capsules it is possible to use, for example, lactose, starch,for example maize starch, or starch derivatives, talc, stearic acid orits salts, etc. Carriers for soft gelatin capsules and suppositoriesare, for example, fats, waxes, semisolid and liquid polyols, natural orhardened oils, etc. Suitable carriers for the preparation of solutions,for example of solutions for injection, or of emulsions or syrups are,for example, water, physiologically sodium chloride solution, alcoholssuch as ethanol, glycerol, polyols, sucrose, invert sugar, glucose,mannitol, vegetable oils, etc. It is also possible to lyophilize thecompounds of the formula (I) and their pharmaceutically acceptable saltsand to use the resulting lyophilizates, for example, for preparingpreparations for injection or infusion. Suitable carriers formicrocapsules, implants or rods are, for example, copolymers of glycolicacid and lactic acid.

Besides the compound or compounds according to the invention andcarriers, the pharmaceutical preparations can also contain additives,for example fillers, disintegrants, binders, lubricants, wetting agents,stabilizers, emulsifiers, dispersants, preservatives, sweeteners,colorants, flavorings, aromatizers, thickeners, diluents, buffersubstances, solvents, solubilizers, agents for achieving a depot effect,salts for altering the osmotic pressure, coating agents or antioxidants.

The dosage of the compound of the formula (I) to be administered and/orof a pharmaceutically acceptable salt thereof depends on the individualcase and is, as is customary, to be adapted to the individualcircumstances to achieve an optimum effect. Thus, it depends on thenature and the severity of the disorder to be treated, and also on thesex, age, weight and individual responsiveness of the human or animal tobe treated, on the efficacy and duration of action of the compoundsused, on whether the therapy is acute or chronic or prophylactic, or onwhether other active compounds are administered in addition to compoundsof the formula (I). In general, a daily dose of approximately 0.01 to100 mg/kg, preferably 0.1 to 10 mg/kg, in particular 0.3 to 5 mg/kg (ineach case mg per kg of bodyweight) is appropriate for administration toan adult weighing approximately 75 kg in order to obtain the desiredresults. The daily dose can be administered in a single dose or, inparticular when larger amounts are administered, be divided intoseveral, for example two, three or four individual doses. In some cases,depending on the individual response, it may be necessary to deviateupwards or downwards from the given daily dose.

The compounds according to the formula (I) can also be used for otherpurposes than those indicated in the foregoing. Non-limiting examplesinclude diagnostic purposes, use as biochemical tools, and asintermediates for the preparation of further compounds, e.g.pharmaceutically active compounds.

The present invention will now be illustrated in the following examples:

EXAMPLES General Procedures

Method A

0.5 mmol of the respective tetrahydronaphthyl amine were dissolved in 10ml 1,2-dichloroethane, 41 μl (0.5 mmol) of pyridine were added, and then1 ml of a 0.55 molar solution of the respective acid chloride in1,2-dichloroethane was added at 0° C., followed by stirring over nightat RT. The thus-obtained mixture was filtered, washed with 5% NaHCO₃—and 5% NaCl-solution, dried over sodium sulfate and concentrated. Thethus-obtained residue was fractionated with prep. HPLC (RP18,acetonitrile/water, 0.1% trifluoroacetic acid).

Unless indicated otherwise, the retention times indicated were obtainedon an Aglint HP 1100 MSD HPLC-system with an Alltech 33×7 mm EPS C18 100Å 1.5 μm-column and a water/acetonitrile-gradient (start: 5% H₂0/95% ofa mixture or H₂O and acetonitrile (10:90); 4.25 min: 5% H₂0/95% of amixture or H₂O and acetonitrile (10:90); 4.5 min: 5% H₂0/95% of amixture or H₂O and acetonitrile (10:90); 5 min: 5% H₂0/95% of a mixtureor H₂O and acetonitrile (10:90) and a flow of 0.75 ml/min.

There were thus obtained:

Ex 1 4-Fluoro-N-(1,2,3,4-tetrahydro-naphth-2-yl)-benzamide

[M+H⁺] measured: 270.0

retention time: 5.07 min (gradient: from 10% acetonitrile to 90%acetonitrile in 10 min)

Ex 2 (R)-N-(6-Bromo-1,2,3,4-tetrahydro-naphth-2-yl)-4-fluoro-benzamide

[M+H⁺] measured: 347.9

retention time: 3.26

Ex 3 (S)-N-(6-Bromo-1,2,3,4-tetrahydro-naphth-2-yl)-4-fluoro-benzamide

[M+H⁺] measured: 347.9

retention time: 3.26

Ex 4 (R)-N-(8-Bromo-1,2,3,4-tetrahydro-naphth-2-yl)-4-fluoro-benzamide

[M+H⁺] measured: 347.9

retention time: 3.25

Ex 5 (S)-N-(8-Bromo-1,2,3,4-tetrahydro-naphth-2-yl)-4-fluoro-benzamide

[M+H⁺] measured: 347.9

retention time: 3.25

Ex 6 (R)-N-(5-Methoxy-1,2,3,4-tetrahydro-naphth-2-yl)-4-fluoro-benzamide

[M+H⁺] measured: 300.0

retention time: 3.12

Ex 7 (S)-N-(5-Methoxy-1,2,3,4-tetrahydro-naphth-2-yl)-4-fluoro-benzamide

[M+H⁺] measured: 300.0

retention time: 3.12

Ex 8 (S)-N-(7-Methoxy-1,2,3,4-tetrahydro-naphth-2-yl)-4-fluoro-benzamide

[M+H⁺] measured: 300.0

retention time: 3.11

Ex 9 (R)-N-(8-Methoxy-1,2,3,4-tetrahydro-naphth-2-yl)-4-fluoro-benzamide

[M+H⁺] measured: 300.0

retention time: 3.13

Method B:

To 0.75 mmol of the respective acid and 271 μl (1.575 mmole)diisopropylethylamine (DIPEA) in 5 ml tetrahydrofuran were added 271 mg(0.825 mmol)O-[(cyano-ethoxycarbonylmethylene)-amino]-N,N,N′,N′-tetramethyluroniumtetrafluoroborate (TOTU) (dissolved in 1 ml DMF). After 15 min stirringat room temperature a mixture of 168 mg (0.900 mmol),2-amino-1,2,3,4-tetrahydronaphthalene hydrochloride in the form of theR- or S-enantiomer and 172 μl (1.000 mmol) DIPEA in 1 ml DMF was added.After stirring for 6 h the mixture was filtered and evaporated. Theresidue was taken up in ethyl acetate and washed successively with 20 ml1 n HCL and 20 ml 5% sodium hydrogencarbonate solution. The resultingorganic phase was evaporated and purified via prep. HPLC. (RP 18,Acetonitrile/Water).

The chromatographic conditions (HPLC) were as follows: LiChroCart 55-2,PuroSpher STAR; RP 18 e (MERCK), solvent A: acetonitrile/water(90:10)+0.5% formic acid; solvent B: acetonitrile/water (10:90)+0.5%formic acid; gradient: 95% B 0.5 min, 95% B to 5% B in 1.75 min, 5% B2.5 min; 1 ml/min.

Ex 10 3-Dimethylamino-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-benzamide

[M+H⁺] measured: 295

retention time: 3.020

Ex 11 3-Dimethylamino-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-benzamide

[M+H⁺] measured: 295

retention time: 3.02

Ex 12 3-Amino-pyrazine-2-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide (salt with formic acid)

[M+H⁺] measured: 269

retention time: 3.03

Ex 13 3-Amino-pyrazine-2-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide (salt with formic acid)

[M+H⁺] measured: 269

retention time: 3.03

Ex 14 6-Chloro-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 287

retention time: 2.98

Ex 15 6-Chloro-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 287

retention time: 2.99

Ex 162-Hydroxy-6-methyl-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 283

Rf-value: 2.80

Ex 17 2-Amino-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 283

retention time: 2.480

Ex 18 2-Amino-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 268

retention time: 2.50

Ex 19 6-Methyl-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide

[M+H⁺] measured: 267

retention time: 2.61

Ex 20 6-Methyl-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide

[M+H⁺] measured: 267

retention time: 2.63

Ex 21 1H-Indole-4-carboxylicacid-N-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 291

retention time: 2.963

Ex 22 1H-Indole-4-carboxylicacid-N-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 291

retention time: 2.97

Ex 23 1H-Benzoimidazole-5-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 292

retention time: 2.523

Ex 24 1H-Benzoimidazole-5-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 292

retention time: 2.54

Ex 25 1H-Benzotriazole-5-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 293

retention time: 2.806

Ex 26 1H-Benzotriazole-5-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 293

retention time: 2.78

Ex 27 2-Methyl-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide;salt with formic acid

[M+H⁺] measured: 267

retention time: 2.509

Ex 28 2-Methyl-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide

[M+H⁺] measured: 267

retention time: 2.46

Ex 29 2,4-Dimethyl-thiazole-5-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 287

retention time: 2.920

Ex 30 2,4-Dimethyl-thiazole-5-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 287

retention time: 2.93

Ex 31 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 332

retention time: 3.065

Ex 32 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 332

retention time: 3.08

Ex 33 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylicacid N-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 420

retention time: 3.294

Ex 34 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylicacid N-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 420

retention time: 3.28

Ex 35 5-Methyl-pyrazine-2-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide (salt with formic acid)

[M+H⁺] measured: 268

retention time: 2.987

Ex 36 5-Methyl-pyrazine-2-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide (salt with formic acid)

[M+H⁺] measured: 268

retention time: 3.00

Ex 372,6-Dimethoxy-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide

[M+H⁺] measured: 313

retention time: 3.283

Ex 382,6-Dimethoxy-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide

[M+H⁺] measured: 313

retention time: 3.24

Ex 392-Chloro-6-methyl-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 301

retention time: 2.941

Ex 402-Chloro-6-methyl-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 301

retention time: 2.97

Ex 41 4-Methyl-2-phenyl-thiazole-5-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 349

retention time: 3.285

Ex 42 4-Methy)-2-phenyl-thiazole-5-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 349

retention time: 3.31

Ex 432-Amino-4,6-dimethyl-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide

[M+H⁺] measured: 296

retention time: 2.410

Ex 442-Amino-4,6-dimethyl-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 296

retention time: 2.40

Ex 45 2-Methyl-4-trifluoromethyl-thiazole-5-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 341

retention time: 3.076

Ex 46 2-Methyl-4-trifluoromethyl-thiazole-5-carboxylicacid-N-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 341

retention time: 3.07

Ex 47 5-Trifluoromethyl-thieno[3,2-b]pyridine-6-carboxylicacid-N-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide (salt with formicacid)

[M+H⁺] measured: 377

retention time: 3.083

Ex 48 1H-Indole-6-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 291

retention time: 2.990

Ex 49 1H-Indole-6-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 291

retention time: 3.02

Ex 50N-(R)-1,2,3,4-Tetrahydro-naphthalen-2-yl-6-trifluoromethyl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 321

retention time: 3.075

Ex 51N-(S)-1,2,3,4-Tetrahydro-naphthalen-2-yl-6-trifluoromethyl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 321

Rf-value: 3.09

Ex 52 2-Methyl-1H-benzoimidazole-5-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 306

retention time: 2.507

Ex 53 2-Methyl-1H-benzoimidazole-5-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 306

retention time: 2.46

Ex 542-Methyl-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-6-trifluoromethyl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 335

retention time: 3.095

Ex 552-Methyl-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-6-trifluoromethyl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 335

retention time: 3.10

Ex 56 6-Cyano-N-(R)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 278

retention time: 2.946

Ex 57 6-Cyano-N-(S)-1,2,3,4-tetrahydro-naphthalen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 278

retention time: 2.93

Ex 58 3,5-Dimethyl-1H-pyrazole-4-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 270

retention time: 2.735

Ex 59 3,5-Dimethyl-1H-pyrazole-4-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 270

retention time: 2.76

Ex 60 1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 362

retention time: 3.053

Ex 61 1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 362

retention time: 3.06

Ex 62N-(R)-1,2,3,4-Tetrahydro-naphthalen-2-yl-5-thiophen-2-yl-nicotinamide

[M+H⁺] measured: 335

retention time: 3.063

Ex 63N-(S)-1,2,3,4-Tetrahydro-naphthalen-2-yl-5-thiophen-2-yl-nicotinamide(salt with formic acid)

[M+H⁺] measured: 335

retention time: 3.08

Ex 64 Benzo[c]isoxazole-3-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 293

retention time: 3.149

Ex 65 Benzo[c]isoxazole-3-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 293

retention time: 3.17

Ex 66 1-(3,5-Dichloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic acidN-(R)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 429

retention time: 3.558

Ex 67 1-(3,5-Dichloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic acidN-(S)-(1,2,3,4-tetrahydro-naphthalen-2-yl)-amide

[M+H⁺] measured: 429

retention time: 3.54

Ex 68 (R)-N-(1,2,3,4-Tetrahydro-naphthalen-2-yl)-isonicotinamide (saltwith formic acid)

[M+H⁺] measured: 335

retention time: 2.695

Ex 69 (S)-N-(1,2,3,4-Tetrahydro-naphthalen-2-yl)-isonicotinamide (saltwith formic acid)

[M+H⁺] measured: 335

retention time: 3.08

Measurement of Activation of eNOS Transcription

Activation of eNOS transcription was measured as described in detail inLi et al. “Activation of protein kinase C alpha and/or epsilon enhancestranscription of the human endothelial nitric oxide synthase gene”, Mol.Pharmacol. 1998; 53: 630-637. Briefly, a 3.5 kB long fragment 5′ of thestarting codon of the eNOS gene was cloned, sequenced and cloned infirefly luciferase expression plasmids to monitor activation of the eNOSpromoter by reporter gene activity. A human endothelial cell line stabletransfected and expressing this promoter-reporter construct was used forcompound testing. Cells were incubated for 18 h with compounds.

All compounds were dissolved in sterile DMSO. A final concentration of0.5% DMSO in complete medium was allowed. Induction of reporter geneexpression in these cells was measured using a standard luciferase assaysystem (Promega, Cat. No E150) according to the manufacturer'sinstructions. Luciferase induction in cells incubated with compoundswere compared to those incubated with solvent alone. The ratio of bothactivities (transcription induction ratio, TIR) was plotted as afunction of compound concentration. Typically, TIR values started at lowconcentrations at a ratio of 1, indicating no compound effect, andextended up to a maximum TIR value TIR(max) which indicates the increaseof the eNOS transcription. EC50 values of transcription induction ratiosas a function of compound concentration were determined graphically.

The effect of compounds on eNOS-transcription was confirmed in a secondassay based on eNOS protein detection. Primary human umbilical vein cordendothelial cells (HUVEC) were isolated and cultivated according tostandard procedures. Confluent cells were incubated with compounds for18 h and the effect on eNOS protein expression determined by aquantitative Western blotting procedure. After incubation with thecompounds, HUVEC were lyzed in ice-cold lysis buffer containing 10 mMTris-HCl, pH 8.0, 1% SDS and protease inhibitors. The lyzate wassubjected to a standard denaturating polyacrylamid gel electropheresisand blotted to nitrocellulose membranes. Using a specific primarymonoclonal antibody (Transduction Laboratories, UK) and alkalinephosphatase labelled secondary antibody (Jackson Labs), a specific eNOSprotein band was visualized and quantified based on a chemifluorescencedetection method.

The results are shown in the table below

EC-50 Compound No: (μM) 1 2.2 4 >30 5 10 6 1.5 7 6 10 9.56 11 12.80 145.93 17 1.96 19 10.89 20 24.71 22 8.82 23 11.50 25 4.55 26 15.05 27 0.1829 10.46 30 81.83 31 10.92 32 1.13 33 7.00 34 9.97 35 14.87 36 0.33 3928.30 40 13.55 41 20.35 42 15.97 43 20.59 45 0.29 46 0.41 47 35.25 4815.64 50 24.56 51 1.60 52 24.35 54 16.33 55 1.10 56 2.75 57 0.50 60 4.1262 4.47 63 0.30 64 15.19 66 5.86 67 23.48 69 0.19

The effect of the compounds according to the invention can also beinvestigated in the following animal models. (Animal experiments areperformed in accordance to the German animal protection law and to theguidelines for the use of experimental animals as given by the Guide forthe Care and Use of Laboratory Animals of the US National Institutes ofHealth.)

Animals and Treatment (Experiments A-C)

ApoE and eNOS deficient mice (C57BL/6J background, Jackson Laboratory,Bar Harbor, Me.) are used. All animals are 10-12 weeks of age and weigh22 to 28 g. Three days before surgery mice are divided into 4 groups(apoE control, n=10-12; apoE with test compounds, n=10-12; eNOS control,n=10-12; eNOS with test compounds, n=10-12) and receive either astandard rodent chow (containing 4% fat and 0.001% cholesterol; in thefollowing designated as placebo group) or a standard rodent chow+testcompound (10 or 30 mg/kg/d p.o.).

A Anti-hypertensive Effect in ApoE Knockout Mice

Blood-pressure is determined in conscious mice using a computerizedtail-cuff system (Visitech Systems, Apex, N.C.). After treatment of ApoEdeficient mice and eNOS deficient mice with the test compounds the bloodpressure is compared to the results obtained with a placebo treatment.

B Inhibition of Neointima Formation and Atherogenesis (femoral arterycuff)

After a 3 day treatment of ApoE deficient mice with the respectivecompound, (10 mg/kg/d pressed in chow), animals are anesthetized with anintraperitoneal injection of pentobarbital (60 mg/kg) followed by anintramuscular injection of xylazin (2 mg/kg) and a cuff is placed aroundthe femoral artery as described in Moroi et al.(J Clin Invest.101:1225-32, 1998). Briefly, the left femoral artery is dissected. Anon-occlusive 2.0 mm polyethylene cuff made of PE-50 tubing (innerdiameter 0.56 mm, outer diameter 0.965 mm, Becton Dickinson, MountainView, Calif.) is placed around the artery and tied in place with two 7-0sutures. The right femoral artery is isolated from the surroundingtissues but a cuff is not placed. Treatment with the respective compoundis continued for 14 days after surgery. Then the animals are sacrificed.The aorta are taken for determination of vascular eNOS expressions byquantitative western blotting. Both femoral arteries are harvested,fixed in formalin and embedded in paraffin. 20 cross sections (10 μm)are cut from the cuffed portion of the left femoral artery and from thecorresponding segment of the right artery. Sections are subjected tostandard hematoxylin and eosin staining. Morphometric analyses areperformed using an image analysis computer program (LeicaQWin, LeicaImaging Systems, Cambridge, GB). For each cross section the area of thelumen, the neointima and the media are determined. To this end, theneointima is defined as the area between the lumen and the internalelastic lamina and the media is defined as the area between the internaland the external elastic lamina. The ratio between the area of theneointima and the area of the media is expressed as the neointima/mediaratio. The results obtained in the compound group are compared to thoseobtained in the placebo group.

C Prevention of Atherosclerotic Plaque Formation in Chronic Treatment

ApoE deficient mice are treated for 16 weeks with the respectivecompound pressed in chow and finally sacrificed. Aortas are removed fromeach mouse, fixed in formalin and embedded in paraffin. Plaque formationis measured via lipid lesions formation in the aortas (from aortic archto diaphragm) and is analyzed by oil red O staining. For quantifying theeffect of the respective compound on vascular eNOS expression thefemoral arteries are used in this experiment. The results obtained inthe compound group are compared to those obtained in the placebo group.

D Improvement of Coronary Function in Diseased ApoE Deficient Mice

Old Male wild-type C57BL/6J mice (Charles River Wiga GmbH, Sulzfeld),and apoE deficient mice (C57BL/6J background, Jackson Laboratory, BarHarbor, Me.) 6 month of age and weighing 28 to 36 g are used in theexperiments. Mice are divided into 3 groups (C57BL/6, n=8; apoE control,n=8; apoE with respective compound, n=8) and receive for 8 weeks eithera standard rodent chow (containing 4% fat and 0.001% cholesterol) or astandard rodent chow+respective compound (30 mg/kg/d p.o.).

Mice are anesthetized with sodium pentobarbitone (100 mg/kg i.p.), andthe hearts are rapidly excised and placed into ice-cold perfusionbuffer. The aorta is cannulated and connected to a perfusion apparatus(HUGO SACHS ELECTRONICS, Freiburg, Germany) which is started immediatelyat a constant perfusion pressure of 60 min Hg. Hearts are perfused in aretrograde fashion with modified Krebs bicarbonate buffer, equilibratedwith 95% O₂ and 5% CO₂ and maintained at 37.5° C.

A beveled small tube (PE 50) is passed through a pulmonary vein into theleft ventricle and pulled through the ventricular wall, anchored in theapex by a fluted end, and connected to a tip-micromanometer (Millar 1.4French). The left atrium is cannulated through the same pulmonary veinand the heart switched to the working mode with a constant preloadpressure of 10 mm Hg and an afterload pressure of 60 mm Hg. Aorticoutflow and atrial inflow are continuously measured using ultrasonicflow probes (HSE/Transonic Systems Inc.). Coronary flow is calculated asthe difference between atrial flow and aortic flow. All hemodynamic dataare digitized at a sampling rate of 1000 Hz and recorded with a PC usingspecialized software (HEM, Notocord).

Hearts are allowed to stabilize for 30 min. All functional hemodynamicdata are measured during steady state, and during volume- and pressureloading.

Left ventricular function curves are constructed by varying pre-loadpressure. For acquisition of preload curves, afterload is set at 60 mmHg and preload is adjusted in 5 mm Hg steps over a range of 5 to 25 mmHg. Hearts are allowed to stabilize at baseline conditions betweenpressure- and volume-loading.

1. An acylated 1,2,3,4-tetrahydronaphthyl amine according to the generalformula (I) in any of its stereoisomeric forms or a mixture thereof inany ratio or a pharmaceutically acceptable salt thereof

wherein R¹ and R⁴ are independently of each other chosen from: H;unsubstituted and at least monosubstituted C₁-C₁₀-alkyl, C₂-C₁₀-alkenyland C₂-C₁₀-alkynyl, the substituents of which are chosen from F, OH,C₁-C₈-alkoxy, (C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃;R⁹CO; CONR¹⁰R¹¹; COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵;S(O)_(m)R¹⁶; SO₂NR¹⁷R¹⁸; and NO₂; R₂ and R₃ are independently of eachchosen from: H; halogens; pseudohalogens; unsubstituted and at leastmonosubstituted C₁-C₁₀-alkyl the substituents of which are chosen fromOH, phenyl, and heteroaryl; OH; C₁-C₁₀-alkoxy; phenoxy; S(O)_(m)R¹⁹;CF₃; CN; NO₂; (C₁-C₁₀-alkyl)amino; di(C₁-C₁₀-alkyl)amino;(C₁-C₆-alkyl)-CONH—; unsubstituted and at least monosubstitutedphenyl-CONH— and phenyl-SO₂—O—, the substituents of which are chosenfrom halogens, pseudohalogens, CH₃ and methoxy; (C₁-C₆-alkyl)SO₂—O—;unsubstituted and at least monosubstituted (C₁-C₆-alkyl)CO, thesubstituents of which are chosen from F, di(C₁-C₃-alkyl)amino,pyrrolidinyl and piperidinyl; and phenyl-CO, the phenyl part of whichcan be substituted by one or more substituents chosen from C₁-C₃-alkyl,halogens and methoxy; A is chosen from CH₂, CHOH and CH—(C₁-C₃-alkyl); Bis chosen from CH₂ and CH—(C₁-C₃-alkyl); C independently has the samemeaning as B; R⁵ is a group Hetar which can be unsubstituted or carryone or more substituents chosen from: halogens; pseudohalogens; NH₂;unsubstituted and at least monosubstituted C₁-C₁₀-alkyl, C₂-C₁₀-alkenyl,C₂-C₁₀-alkynyl, C₁-C₁₀-alkoxy, (C₁-C₁₀-alkyl)amino, anddi(C₁-C₁₀-alkyl)amino, the substituents of which are chosen from F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino,and di(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;aryl-substituted C₁-C₄-alkyl; heteroaryl-substituted C₁-C₄-alkyl; CF₃;NO₂; OH; phenoxy; benzyloxy; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH;phenylamino; benzylamino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR²⁴R²⁵; R²⁶SO₂NH—; R²⁷SO₂N(C₁-C₆-alkyl)-; andsaturated and at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms chosen from N, O,and S, which heterocycles can be substituted by one or more substituentschosen from halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, andwherein said heterocycles can optionally be condensed to said groupHetar; and wherein all aryl, heteroaryl, phenyl, aryl-containing,heteroaryl-containing and phenyl-containing groups, which are optionallypresent in said substituents of said group Hetar, can be substituted byone or more substituents chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; R⁶ is chosen from: H;C₁-C₁₀-alkyl, which can be substituted by one or more substituentschosen from F, C₁-C₈-alkoxy, and di(C₁-C₈-alkyl)amino;aryl-(C₁-C₄-alkyl) and heteroaryl-(C₁-C₄-alkyl), which can besubstituted by one or more substituents chosen from halogens,C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino; R⁷ is chosen from: H;C₁-C₁₀-alkyl which can be substituted by one or more substituents,chosen from F, C₁-C₈-alkoxy, di(C₁-C₈-alkyl)amino and phenyl; phenyl;indanyl; and heteroaryl; and wherein each of the aforementioned aromaticgroups can be unsubstituted or carry one or more substituents chosenfrom halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁸ isH or C₁-C₁₀-alkyl; R⁹ is chosen from: C₁-C₁₀-alkyl which can beunsubstituted or carry one or more substituents chosen from F,(C₁-C₄)-alkoxy, di(C₁-C₃-alkyl)amino; and unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from C₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, andCF₃; R¹⁰ independently has the same meaning as R⁷; R¹¹ independently hasthe same meaning as R⁸; R¹² independently has the same meaning as R⁶;R¹³ is chosen from H; C₁-C₆-alkyl; unsubstituted and substituted phenyl,benzyl, heteroaryl, (C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁴ independently has the same meaning asR¹³; R¹⁵ is chosen from H; C₁-C₁₀-alkyl; (C₁-C₃-alkoxy)-C₁-C₃-alkyl; andsubstituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁶ is chosen from C₁-C₁₀-alkyl which canbe substituted by one or more substituents chosen from F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, (C₁-C₈-alkyl)amino anddi(C₁-C₈-alkyl)amino; CF₃, and substituted and unsubstituted phenyl andheteroaryl, the substituents of which are chosen from halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one ormore of these substitutents can be present; R¹⁷ independently has thesame meaning as R⁷; R¹⁸ independently has the same meaning as R⁸; R¹⁹independently has the same meaning as R¹⁶; R²⁰ independently has thesame meaning as R¹⁶; R²¹ independently has the same meaning as R⁶; R²²independently has the same meaning as R⁷; R²³ independently has the samemeaning as R⁸; R²⁴ independently has the same meaning as R⁷; R²⁵independently has the same meaning as R⁸; R²⁶ independently has the samemeaning as R¹⁶; R²⁷ independently has the same meaning as R¹⁶;heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;aryl is phenyl, naphth-1-yl or naphth-2-yl; m is 0, 1 or 2; with theproviso that, in case R¹, R², R³ and R⁴ are hydrogen or one of thesubstituents, R¹ R², R³ or R⁴ is C₁-C₆-alkoxy, R⁵ is not unsubstitutedpyridyl or unsubstituted or substituted 4-oxoquinolinyl; where one ofthe groups R¹ and R² is hydroxy and the other groups of R¹, R², R³, andR⁴ are hydrogen, R⁵ is not unsubstituted pyridyl; and where groups A, B,and C are each CH², R⁵ is not 5-nitrofuryl.
 2. An acylated1,2,3,4-tetrahydronaphthyl amine in any of its stereoisomeric forms or amixture thereof in any ratio or a pharmaceutically acceptable saltthereof according to claim 1, wherein in the formula (I) R¹ is chosenfrom H; C₁-C₄-alkyl; C₁-C₄-alkoxy; CF₃; halogens; pseudohalogens;(C₁-C₄-alkyl)-S(O)_(m)—; and unsubstituted and at least monosubstitutedphenyl and heteroaryl, the substituents of which are chosenfromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, andwherein heteroaryl is chosen from 5- and 6-membered heterocyclescontaining one or more heteroatoms chosen from N, O, and S; R² and R³are independently of each other chosen from: H; halogens;pseudohalogens; and C₁-C₃-alkyl; R⁴ independently has the same meaningas R¹; A is chosen from CH₂ and CHOH; B and C are independently of eachother chosen from CH₂ and CH—CH₃; R⁵ is a group Hetar which can beunsubstituted or carry one or more substituents chosen from: halogens;CN; NH₂; unsubstituted and at least monosubstituted C₁-C₈-alkyl,C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₁-C₈-alkoxy, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino, the substituents of which are chosen from F,C₁-C₆-alkoxy, phenoxy, (C₁-C₆-alkyl)mercapto, NH₂, (C₁-C₆-alkyl)amino,and di(C₁-C₆-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;phenyl-substituted C₁-C₂-alkyl; heteroaryl-substituted C₁-C₂-alkyl; CF₃;OH; phenoxy; benzyloxy; (C₁-C₆-alkyl)COO; S(O)_(m)(C₁-C₆)-alkyl;S(O)_(m)-phenyl; S(O)_(m)-heteroaryl; SH; phenylamino; benzylamino;(C₁-C₆-alkyl)-CONH—; (C₁-C₆-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₆-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—;COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₆-alkyl); —CON(di(C₁-C₆-alkyl));CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₆-alkyl); —SO₂NH(phenyl);—SO₂N(di(C₁-C₆-alkyl)); (C₁-C₆-alkyl)SO₂NH—;(C₁-C₆-alkyl)SO₂N(C₁-C₆-alkyl)-; phenyl-SO₂NH—;phenyl-SO₂N(C₁-C₆-alkyl)-; heteroaryl-SO₂NH—;heteroaryl-SO₂N(C₁-C₆-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo, and CF₃, and wherein saidheterocycles can optionally be condensed to said group Hetar; andwherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said group Hetar, can be substituted by one or moresubstituents chosen from halogens, pseudohalogens, C₁-C₃-alkyl, OH,C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to 10-membered, aromatic, mono-or bicyclic heterocycle containing one or more heteroatoms chosen fromN, O, and S; the group Hetar is a 5 to 10-membered, aromatic, mono- orbicyclic heterocycle containing one or more heteroatoms chosen from N, Oand S; and m is O or
 2. 3. An acylated 1,2,3,4-tetrahydronaphthyl aminein any of its stereoisomeric forms or a mixture thereof in any ratio ora pharmaceutically acceptable salt thereof according to claim 1, whereinin the formula (I) R¹ is H, halogen or C₁-C₄-alkyl; R² and R³ are eachH; R⁴ independently has the same meaning as R¹; A is CH₂; R⁵ is a groupHetar which can be unsubstituted or carry one or more substituentschosen from: halogens; CN; NH₂; unsubstituted and at leastmonosubstituted C₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₃-alkoxy,(C₁-C₄-alkyl)amino, and di(C₁-C₄-alkyl)amino, the substituents of whichare chosen from F, C₁-C₃-alkoxy, (C₁-C₃-alkyl)mercapto, and NH₂;C₃-C₅-alkandiyl; phenyl; heteroaryl; phenyl-substituted C₁-C₂-alkyl;heteroaryl-substituted C₁-C₂-alkyl; CF₃; OH; (C₁-C₄-alkyl)COO;S(O)_(m)(C₁-C₄)-alkyl; (C₁-C₄-alkyl)-CONH—;(C₁-C₄-alkyl)-CON(C₁-C₄-alkyl)-; (C₁-C₄-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF2O—; —OCH₂CH₂O—; —CH₂CH₂O—;COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl));CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂NH(phenyl);—SO₂N(di(C₁-C₄-alkyl)); (C₁-C₄-alkyl)SO₂NH—;(C₁-C₄-alkyl)SO₂N(C₁-C₄-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, and wherein saidheterocycles can optionally be condensed to said group Hetar; andwherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said group Hetar, can be substituted by one or moresubstituents chosen from halogens, pseudohalogens, C₁-C₃-alkyl, OH,C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to 10-membered, aromatic, mono-or bicyclic heterocycle containing one, two or three heteroatoms chosenfrom N, O, and S; the group Hetar is a 5 to 10-membered, aromatic, mono-or bicyclic heterocycle containing one, two or three heteroatoms chosenfrom N, O, and S; and m is 0 or
 2. 4. The acylated1,2,3,4-tetrahydronaphthyl amine in any of its stereoisomeric forms or amixture thereof in any ratio or a pharmaceutically acceptable saltthereof according to claim 1, wherein in the formula (I) R¹ is H,halogen or C₁-C₄-alkyl; R² and R³ are each H; R⁴ independently has thesame meaning as R¹; A and B are each CH₂; C is CH₂ or CH—CH₃; R⁵ is agroup Hetar which can be unsubstituted or carry one or more substituentschosen from: F; Cl; Br; C₁-C₃-alkyl; C₁-C₃-alkoxymethyl;2-amino-3,3,3-trifluoro-propyl-; CF₃; C₃-C₅-alkandiyl; phenyl;heteroaryl; benzyl; heteroaryl-methyl; OH; C₁-C₃-alkoxy; phenoxy;trifluoromethoxy; 2,2,2-trifluoroethoxy; (C₁-C₄-alkyl)COO;(C₁-C₃-alkyl)mercapto; phenylmercapto; (C₁-C₃-alkyl)sulfonyl;phenylsulfonyl; NH₂; (C₁-C₄-alkyl)amino; di(C₁-C₄-alkyl)amino;(C₁-C₃-alkyl)-CONH—; (C₁-C₃-alkyl)-SO₂NH—; (C₁-C₃-alkyl)-CO; phenyl-CO;—OCH₂O—; —OCF₂O—; —CH₂CH₂O—; COO(C₁-C₄-alkyl); —CONH₂;—CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl)); CN; —SO₂NH₂;—SO₂NH(C₁-C₄-alkyl); —SO₂N(di(C₁-C₄-alkyl)); pyrrolidinyl; piperidinyl;morpholinyl; and thiomorpholinyl; and wherein all heteroaryl, phenyl,heteroaryl-containing and phenyl-containing groups, which are optionallypresent in said substituents of said group Hetar, can be substituted byone or more substituents chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; heteroaryl is chosen from:furyl, pyrrolyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl,pyrazolyl, imidazolyl, pyridazinyl, pyrazinyl, pyridyl, pyrimidinyl,benzoimidazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl,quinoxalinyl, quinazolyl, indolyl, benzofuranyl, benzothiophenyl, andindazolyl; the group Hetar is chosen from: furyl, pyrrolyl, thienyl,thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl,pyridazinyl, pyrazinyl, pyridyl, pyrimidinyl, benzoimidazolyl,benzothiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, quinoxalinyl,quinazolyl, indolyl, benzofuranyl, benzothiophenyl, and indazolyl.
 5. Anacylated 1,2,3,4-tetrahydronaphthyl amine according to the generalformula (I) in any of its stereoisomeric forms or a mixture thereof inany ratio or a pharmaceutically acceptable salt thereof

wherein R¹ is H, halogen or C₁-C₄-alkyl; R² and R³ are each H; R⁴independently has the same meaning as R¹; A and B are each CH₂; C is CH₂or CH—CH₃; R⁵ is chosen from: benzo[1,3]dioxol-5-yl,2,2-difluoro-benzo[1,3]dioxol-5-yl, 2,3-dihydrobenzofuran-5-yl,1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-yl,1-(4-fluoro-phenyl)-3,5-dimethyl-1H-pyrazole-4-yl,1H-benzotriazole-5-yl, 1H-indole-4-yl, 1H-indole-6-yl,1-isopropyl-2-trifluoromethyl-1H-benzoimidazole-5-yl,1-methyl-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-yl,1-phenyl-5-trifluoromethyl-1H-pyrazole-4-yl,2-(2-hydroxy-pyridin-4-yl)-1H-benzoimidazole-5-yl,2-(4-cyano-phenyl)-1H-benzoimidazole-5-yl, 2,4-dimethyl-oxazole-5-yl,2,4-dimethyl-pyrimidine-5-yl, 2,4-dimethyl-thiazole-5-yl,2,5-dimethyl-1H-pyrrole-3-yl, 2,5-dimethyl-1-phenyl-1H-pyrrole-3-yl,2,5-dimethyl-1-pyridin-4-ylmethyl-1H-pyrrolyl,2,5-dimethyl-2H-pyrazole-3-yl, 2,6-dichloro-pyrid-3-yl,2,6-dimethoxy-pyrid-3-yl, 2,6-dimethyl-pyrid-3-yl,2-amino-4,6-dimethyl-pyrid-3-yl, 2-amino-6-chloro-pyrid-3-yl,2-amino-pyrid-3-yl, 2-chloro-6-methyl-pyrid-3-yl, 2-chloro-pyrid-4-yl,2-cyclopropyl-4-methyl-thiazole-5-yl,2-dimethylamino-4-methyl-thiazole-5-yl, 2-dimethylamino-pyrid-4-yl,2-ethyl-5-methyl-2H-pyrazole-3-yl, 2-hydroxy-6-methyl-pyrid-3-yl,2-methyl-1H-benzoimidazole-5-yl, 2-methyl-3H-benzoimidazole-5-yl,2-methyl-pyrid-3-yl, 2-methyl-6-trifluoromethyl-pyrid-3-yl,2-methyl-thiazole-5-yl, 2-morpholin-4-yl-pyridin-4-yl,2-morpholin-4-yl-pyrimidine-5-yl, 2-pyrrolidin-1-yl-pyridin-4-yl,3,5-dimethyl-1H-pyrazole-4-yl, 3-amino-5,6-dimethyl-pyrazine-2-yl,3-amino-5-methyl-pyrazine-2-yl, 3-amino-pyrazine-2-yl,3H-benzoimidazole-5-yl, 1H-benzoimidazole-5-yl, 3-methyl-isoxazole-4-yl,4,6-dimethyl-pyrid-3-yl, 4-amino-2-ethylsulfanyl-pyrimidine-5-yl,4-amino-2-methyl-pyrimidine-5-yl, 4-methyl-thiazole-5-yl, pyridine-2-yl,pyridine-3-yl, pyridine-4-yl, 5-thiophen-2-yl-pyrid-3-yl,2-methyl-4-trifluoromethyl-thiazol-5-yl,5,6,7,8-tetrahydro-quinoline-3-yl, 5-amino-1-phenyl-1H-pyrazole-4-yl,5-methyl-1-phenyl-1H-pyrazole-4-yl, 5-methyl-isoxazole-3-yl,5-methyl-pyrid-3-yl, 5-methyl-pyrazine-2-yl, 6-chloro-pyrid-3-yl,6-cyano-pyrid-3-yl, 6-dimethylamino-pyrid-3-yl, 6-ethynyl-pyrid-3-yl,6-methoxymethyl-pyrid-3-yl, 6-methoxy-pyrid-3-yl,6-methyl-2-methylamino-pyrid-3-yl, 6-methylamino-pyrazine-2-yl,6-methyl-pyrid-3-yl, 6-morpholin-4-yl-pyrid-3-yl,6-pyrrolidin-1-yl-pyrid-3-yl, imidazo[1,2-a]pyridine-2-yl,6-trifluoromethyl-pyrid-3-yl, and pyrimidine-4-yl.
 6. A method forsynthesis of a compound according to claim 1, which method comprises thecoupling reaction of the respective 1,2,3,4-tetrahydronaphthyl aminewith a respective acid or acid chloride in the presence of anappropriate base and/or an appropriate coupling agent, optionallyfollowed by a functionalization of the thus-obtained compound.
 7. Apharmaceutical preparation comprising an effective dose of at least onecompound of the formula (I) as defined in claim 1 in any of itsstereoisomeric forms or a mixture thereof in any ratio and/or apharmaceutically acceptable salt thereof and a pharmaceuticallyacceptable carrier.
 8. A pharmaceutical preparation according to claim7, which pharmaceutical preparation is in the form of a pill, tablet,lacquered tablet, sugar-coated tablet, granule, hard or soft gelatincapsule, aqueous, alcoholic or oily solution, syrup, emulsion orsuspension, suppository, solution for injection or infusion, ointment,tincture, spray, transdermal therapeutic systems, nasal spray, aerosolmixture, microcapsule, implant or rod.
 9. A method of stimulating theexpression of endothelial NO-synthase in a mammal, which methodcomprises administering said mammal a physiologically active amount of acompound according to the general formula (I) in any of itsstereoisomeric forms or a mixture thereof in any ratio or apharmaceutically acceptable salt thereof

wherein, in the formula (I), R¹ and R⁴ are independently from each otherchosen from: H; unsubstituted and at least monosubstituted C₁-C₁₀-alkyl,C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents of which are chosenfrom F, OH, C₁-C₈-alkoxy, (C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃;R⁹CO; CONR¹⁰R¹¹; COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵;S(O)_(m)R₁₆; SO₂NR¹⁷R¹⁸; and NO₂; R² and R³ are independently from eachother chosen from: H; halogens; pseudohalogens; unsubstituted and atleast monosubstituted C₁-C₁₀-alkyl the substituents of which are chosenfrom OH, phenyl, and heteroaryl; OH; C₁-C₁₀-alkoxy; phenoxy;S(O)_(m)R¹⁹; CF₃; CN; NO₂; (C₁-C₁₀-alkyl)amino; di(C₁-C₁₀-alkyl)amino;(C₁-C₆-alkyl)-CONH—; unsubstituted and at least monosubstitutedphenyl-CONH— and phenyl-SO₂—O—, the substituents of which are chosenfrom halogens, pseudohalogens, CH₃ and methoxy; (C₁-C₆-alkyl)SO₂—O—;unsubstituted and at least monosubstituted (C₁-C₆-alkyl)CO, thesubstituents of which are chosen from F, di(C₁-C₃-alkyl)amino,pyrrolidinyl and piperidinyl; and phenyl-CO, the phenyl part of whichcan be substituted by one or more substituents chosen from C₁-C₃-alkyl,halogens and methoxy; A is chosen from CH₂, CHOH and CH—(C₁-C₃-alkyl); Bis chosen from CH₂ and CH—(C₁-C₃-alkyl); C independently has the samemeaning as B; R⁵ is a group Ar or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: halogens;pseudohalogens; NH₂; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, C₁-C₁₀-alkoxy,(C₁-C₁₀-alkyl)amino, and di(C₁-C₁₀-alkyl)amino, the substituents ofwhich are chosen from F, OH, C₁-C₈-alkoxy, aryloxy,(C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;aryl-substituted C₁-C₄-alkyl; heteroaryl-substituted C₁-C₄-alkyl; CF₃;NO₂; OH; phenoxy; benzyloxy; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH;phenylamino; benzylamino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR²⁴R²⁵; R²⁶SO₂NH—; R³⁷SO₂N(C₁-C₆-alkyl)-; andsaturated and at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms chosen from N, O,and S, which heterocycles can be substituted by one or more substituentschosen from halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, andwherein said heterocycles can optionally be condensed to said group Aror said group Hetar; and wherein all aryl, heteroaryl, phenyl,aryl-containing, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said group Ar orsaid group Hetar, can be substituted by one or more substituents chosenfrom halogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;R⁶ is chosen from: H; C₁-C₁₀-alkyl, which can be substituted by one ormore substituents chosen from F, C₁-C₈-alkoxy, and di(C₁-C₈-alkyl)amino;aryl-(C₁-C₄-alkyl) and heteroaryl-(C₁-C₄-alkyl), which can besubstituted by one or more substituents chosen from halogens,C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino; R⁷ is chosen from: H;C₁-C₁₀-alkyl which can be substituted by one or more substituents chosenfrom F, C₁-C₈-alkoxy, di(C₁-C₈-alkyl)amino and phenyl; phenyl; indanyl;and heteroaryl; and wherein each of the aforementioned aromatic groupscan be unsubstituted or carry one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁸ is H orC₁-C₁₀-alkyl; R⁹ is chosen from: C₁-C₁₀-alkyl which can be unsubstitutedor carry one or more substituents chosen from: F, (C₁-C₄)-alkoxy,di(C₁-C₃-alkyl)amino; and unsubstituted and at least monosubstitutedphenyl and heteroaryl, the substituents of which are chosen fromC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃; R¹⁰independently has the same meaning as R⁷; R¹¹ independently has the samemeaning as R⁸; R¹² independently has the same meaning as R⁶; R¹³ ischosen from: H; C₁-C₆-alkyl; unsubstituted and substituted phenyl,benzyl, heteroaryl, (C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁴ independently has the same meaning asR¹³; R¹⁵ is chosen from: H; C₁-C₁₀-alkyl; (C₁-C₃-alkoxy)-C₁-C₃-alkyl;and substituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁶ is chosen from: C₁-C₁₀-alkyl which canbe substituted by one or more substituents chosen from F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, (C₁-C₈-alkyl)amino anddi(C₁-C₈-alkyl)amino; CF₃; and substituted and unsubstituted phenyl andheteroaryl, the substituents of which are chosen from halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one ormore of these substitutents can be present; R¹⁷ independently has thesame meaning as R⁷; R¹⁸ independently has the same meaning as R⁸; R¹⁹independently has the same meaning as R¹⁶; R²⁰ independently has thesame meaning as R¹⁶; R²¹ independently has the same meaning as R⁶; R²²independently has the same meaning as R⁷; R²³ independently has the samemeaning as R⁸; R²⁴ independently has the same meaning as R⁷; R²⁵independently has the same meaning as R⁸; R²⁶ independently has the samemeaning as R¹⁶; R²⁷ independently has the same meaning as R¹⁶;heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;aryl is phenyl, naphth-1-yl or naphth-2-yl; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0, 1 or
 2. 10. The method accordingto claim 9, wherein in the formula (I) R¹ is chosen from: H;C₁-C₄-alkyl; C₁-C₄-alkoxy; CF₃; halogens; pseudohalogens;(C₁-C₄-alkyl)-S(O)_(m)—; and unsubstituted and at least monosubstitutedphenyl and heteroaryl, the substituents of which are chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and whereinheteroaryl is chosen from 5- and 6-membered heterocycles containing oneor more heteroatoms chosen from N, O, and S; R² and R³ are independentlyfrom each other chosen from: H; halogens; pseudohalogens; andC₁-C₃-alkyl; R⁴ independently has the same meaning as R¹; A is chosenfrom CH₂ and CHOH; B and C are independently from each other chosen fromCH₂ and CH—CH₃; R⁵ is a group Ar or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: halogens;CN; NH₃; unsubstituted and at least monosubstituted C₁-C₈-alkyl,C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₁-C₈-alkoxy, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino, the substituents of which are chosen from F,C₁-C₆-alkoxy, phenoxy, (C₁-C₆-alkyl)mercapto, NH₂, (C₁-C₆-alkyl)amino,and di(C₁-C₆-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;phenyl-substituted C₁-C₂-alkyl; heteroaryl-substituted C₁-C₂-alkyl; CF₃;OH; phenoxy; benzyloxy; (C₁-C₆-alkyl)COO; S(O)_(m)(C₁-C₆)-alkyl;S(O)_(m)-phenyl; S(O)_(m)-heteroaryl; SH; phenylamino; benzylamino;(C₁-C₆-alkyl)-CONH—; (C₁-C₆-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₆-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—;COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₆-alkyl); —CON(di(C₁-C₆-alkyl));CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₆-alkyl); —SO₂NH(phenyl);—SO₂N(di(C₁-C₆-alkyl)); (C₁-C₆-alkyl)SO₂NH—;(C₁-C₆-alkyl)SO₂N(C₁-C₆-alkyl)-; phenyl-SO₂NH—;phenyl-SO₂N(C₁-C₆-alkyl)-; heteroaryl-SO₂NH—;heteroaryl-SO₂N(C₁-C₆-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, and wherein saidheterocycles can optionally be condensed to said group Ar or said groupHetar; and wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said group Ar or said group Hetar, can be substituted byone or more substituents chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one ormore heteroatoms chosen from N, O, and S; the group Hetar is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one ormore heteroatoms chosen from N, O, and S; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0 or
 2. 11. The method according toclaim 9, wherein in the formula (I) R¹ is H, halogen, or C₁-C₄-alkyl; R²and R³ are each H; R⁴ independently has the same meaning as R¹; A isCH₂; R⁵ is phenyl or a group Hetar both of which can be unsubstituted orcarry one or more substituents chosen from: halogens; CN; NH₂;unsubstituted and at least monosubstituted C₁-C₆-alkyl, C₂-C₆-alkenyl,C₂-C₆-alkynyl, C₁-C₃-alkoxy, (C₁-C₄-alkyl)amino, anddi(C₁-C₄-alkyl)amino, the substituents of which are chosen from F,C₁-C₃-alkoxy, (C₁-C₃-alkyl)mercapto, and NH₂; C₃-C₅-alkandiyl; phenyl;heteroaryl; phenyl-substituted C₁-C₂-alkyl; heteroaryl-substitutedC₁-C₂-alkyl; CF₃; OH; (C₁-C₄-alkyl)COO; S(O)_(m)(C₁-C₄)-alkyl;(C₁-C₄-alkyl)-CONH—; (C₁-C₄-alkyl)-CON(C₁-C₄-alkyl)-; (C₁-C₄-alkyl)-CO;phenyl-CO; heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—;—CH₂CH₂O—; COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl);—CON(di(C₁-C₄-alkyl)); CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₄-alkyl);—SO₂NH(phenyl); —SO₂N(di(C₁-C₄-alkyl)); (C₁-C₄-alkyl)SO₂NH—;(C₁-C₄-alkyl)SO₂N(C₁-C₄-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, and wherein saidheterocycles can optionally be condensed to said phenyl or said groupHetar; and wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said phenyl or said group Hetar, can be substituted byone or more substituents chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one, twoor three heteroatoms chosen from N, O, and S; the group Hetar is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one, twoor three heteroatoms chosen from N, O, and S; and m is 0 or
 2. 12. Themethod according to claim 9, wherein in the formula (I) R¹ is H,halogen, or C₁-C₄-alkyl; R² and R³ are each H; R⁴ independently has thesame meaning as R¹; A and B are each CH₂; C is CH₂ or CH—CH₃; R⁵ isphenyl or a group Hetar both of which can be unsubstituted or carry oneor more substituents chosen from: F; Cl; Br; C₁-C₃-alkyl;C₁-C₃-alkoxymethyl; 2-amino-3,3,3-trifluoro-propyl-; CF₃;C₃-C₅-alkandiyl; phenyl; heteroaryl; benzyl; heteroaryl-methyl; OH;C₁-C₃-alkoxy; phenoxy; trifluoromethoxy; 2,2,2-trifluoroethoxy;(C₁-C₄-alkyl)COO; (C₁-C₃-alkyl)mercapto; phenylmercapto;(C₁-C₃-alkyl)sulfonyl; phenylsulfonyl; NH₂; (C₁-C₄-alkyl)amino;di(C₁-C₄-alkyl)amino; (C₁-C₃-alkyl)-CONH—; (C₁-C₃-alkyl)-SO₂NH—;(C₁-C₃-alkyl)-CO; phenyl-CO; —OCH₂O—; —OCF₂O—; —CH₂CH₂O—;COO(C₁-C₄-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl)); CN;—SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂N(di(C₁-C₄-alkyl)); pyrrolidinyl;piperidinyl; morpholinyl; and thiomorpholinyl; and wherein allheteroaryl, phenyl, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said phenyl or saidgroup Hetar, can be substituted by one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;heteroaryl is chosen from: furyl, pyrrolyl, thienyl, thiazolyl,isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl,pyrazinyl, pyridyl, pyrimidinyl, benzoimidazolyl, benzothiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl,indolyl, benzofuranyl, benzothiophenyl, and indazolyl; the group Hetaris chosen from: furyl, pyrrolyl, thienyl, thiazolyl, isothiazolyl,oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl, pyrazinyl,pyridyl, pyrimidinyl, benzoimidazolyl, benzothiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl, indolyl,benzofuranyl, benzothiophenyl, and indazolyl.
 13. The method accordingto claim 9, wherein in the formula (I) R¹ is H, halogen or C₁-C₄-alkyl;R² and R³ are each H; R⁴ independently has the same meaning as R¹; A andB are each CH₂; C is CH₂ or CH—CH₃; R⁵ is chosen from: 4-fluorophenyl,4-chlorophenyl, 4-bromophenyl, 4-(C₁-C₃-alkoxy)-phenyl,4-trifluoromethoxyphenyl, 2-bromo-4-fluorophenyl,2-chloro-4-fluorophenyl, 3,4-dimethylphenyl, 2,4-dimethylphenyl,4-chloro-2-methylphenyl, 2-hydroxy-4-methylphenyl,2-hydroxy-4-ethoxyphenyl, 2-methoxy-4-methylphenyl, 4-phenoxyphenyl,3-fluoro-4-methylphenyl, benzo[1,3]dioxol-5-yl,2,2-difluoro-benzo[1,3]dioxol-5-yl, 2,3-dihydrobenzofuran-5-yl,1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-yl,1-(4-fluoro-phenyl)-3,5-dimethyl-1H-pyrazole-4-yl,1H-benzotriazole-5-yl, 1H-indole-4-yl, 1H-indole-6-yl,1-isopropyl-2-trifluoromethyl-1H-benzoimidazole-5-yl,1-methyl-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-yl,1-phenyl-5-trifluoromethyl-1H-pyrazole-4-yl,2-(2-hydroxy-pyridin-4-yl)-1H-benzoimidazole-5-yl,2-(4-cyano-phenyl)-1H-benzoimidazole-5-yl, 2,4-dimethyl-oxazole-5-yl,2,4-dimethyl-pyrimidine-5-yl, 2,4-dimethyl-thiazole-5-yl,2,5-dimethyl-1H-pyrrole-3-yl, 2,5-dimethyl-1-phenyl-1H-pyrrole-3-yl,2,5-dimethyl-1-pyridin-4-ylmethyl-1H-pyrrolyl,2,5-dimethyl-2H-pyrazole-3-yl, 2,6-dichloro-pyrid-3-yl,2,6-dimethoxy-pyrid-3-yl, 2,6-dimethyl-pyrid-3-yl,2-amino-4,6-dimethyl-pyrid-3-yl, 2-amino-6-chloro-pyrid-3-yl,2-amino-pyrid-3-yl, 2-chloro-6-methyl-pyrid-3-yl, 2-chloro-pyrid-4-yl,2-cyclopropyl-4-methyl-thiazole-5-yl,2-dimethylamino-4-methyl-thiazole-5-yl, 2-dimethylamino-pyrid-4-yl,2-ethyl-5-methyl-2H-pyrazole-3-yl, 2-hydroxy-6-methyl-pyrid-3-yl,2-methyl-1H-benzoimidazole-5-yl, 2-methyl-3H-benzoimidazole-5-yl,2-methyl-pyrid-3-yl, 2-methyl-6-trifluoromethyl-pyrid-3-yl,2-methyl-thiazole-5-yl, 2-morpholin-4-yl-pyridin-4-yl,2-morpholin-4-yl-pyrimidine-5-yl, 2-pyrrolidin-1-yl-pyridin-4-yl,3,5-dimethyl-1H-pyrazole-4-yl, 3-amino-5,6-dimethyl-pyrazine-2-yl,3-amino-5-methyl-pyrazine-2-yl, 3-amino-pyrazine-2-yl,3-dimethylamino-4-methyl-phenyl, 3-dimethylamino-phenyl,3H-benzoimidazole-5-yl, 1H-benzoimidazole-5-yl,3-methanesulfonylamino-2-methyl-phenyl, 3-methanesulfonylamino-phenyl,3-methyl-isoxazole-4-yl, 3-morpholin-4-yl-phenyl,3-piperidin-1-yl-phenyl, 3-pyrrolidin-1-yl-phenyl,4-(2,2,2-trifluoro-ethoxy)-phenyl, 4,6-dimethyl-pyrid-3-yl,4-amino-2-ethyl sulfanyl-pyrimidine-5-yl,4-amino-2-methyl-pyrimidine-5-yl,4-chloro-3-methanesulfonylamino-phenyl, 4-chloro-3-sulfamoyl-phenyl,4-methyl-3-methylamino-phenyl, 4-methyl-thiazole-5-yl, pyridine-2-yl,pyridine-3-yl, pyridine-4-yl, 5-thiophen-2-yl-pyrid-3-yl,2-methyl-4-trifluoromethyl-thiazol-5-yl,5,6,7,8-tetrahydro-quinoline-3-yl, 5-amino-1-phenyl-1H-pyrazole-4-yl,5-methanesulfonyl-2-methyl-phenyl, 5-methyl-1-phenyl-1H-pyrazole-4-yl,5-methyl-isoxazole-3-yl, 5-methyl-pyrid-3-yl, 5-methyl-pyrazine-2-yl,6-chloro-pyrid-3-yl, 6-cyano-pyrid-3-yl, 6-dimethylamino-pyrid-3-yl,6-ethynyl-pyrid-3-yl, 6-methoxymethyl-pyrid-3-yl, 6-methoxy-pyrid-3-yl,6-methyl-2-methylamino-pyrid-3-yl, 6-methylamino-pyrazine-2-yl,6-methyl-pyrid-3-yl, 6-morpholin-4-yl-pyrid-3-yl,6-pyrrolidin-1-yl-pyrid-3-yl, imidazo[1,2-a]pyridine-2-yl,6-trifluoromethyl-pyrid-3-yl, and pyrimidine-4-yl.
 14. The methodaccording to claim 9, wherein the mammal is a human.
 15. A method oftreating a mammal suffering from hypertension wherein the hypertensionis chosen from essential hypertension, pulmonary hypertension, secondaryhypertension, and renovascular hypertension, which method comprisesadministering to said mammal a physiologically active amount of acompound according to the general formula (I), in any of itsstereoisomeric forms or a mixture thereof in any ratio or apharmaceutically acceptable salt thereof

wherein, in the formula (I), R¹ and R⁴ are independently from each otherchosen from: H; unsubstituted and at least monosubstituted C₁-C₁₀-alkyl,C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents of which are chosenfrom F, OH, C₁-C₈-alkoxy, (C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃;R⁹CO; CONR¹⁰R¹¹; COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵;S(O)_(m)R₁₆; SO₂NR¹⁷R¹⁸; and NO₂; R² and R³ are independently from eachother chosen from: H; halogens; pseudohalogens; unsubstituted and atleast monosubstituted C₁-C₁₀-alkyl the substituents of which are chosenfrom OH, phenyl, and heteroaryl; OH; C₁-C₁₀-alkoxy; phenoxy;S(O)_(m)R¹⁹; CF₃; CN; NO₂; (C₁-C₁₀-alkyl)amino; di(C₁-C₁₀-alkyl)amino;(C₁-C₆-alkyl)-CONH—; unsubstituted and at least monosubstitutedphenyl-CONH— and phenyl-SO₂—O—, the substituents of which are chosenfrom halogens, pseudohalogens, CH₃ and methoxy; (C₁-C₆-alkyl)SO₂—O—;unsubstituted and at least monosubstituted (C₁-C₆-alkyl)CO, thesubstituents of which are chosen from F, di(C₁-C₃-alkyl)amino,pyrrolidinyl and piperidinyl; and phenyl-CO, the phenyl part of whichcan be substituted by one or more substituents chosen from C₁-C₃-alkyl,halogens and methoxy; A is chosen from CH₂, CHOH and CH—(C₁-C₃-alkyl); Bis chosen from CH₂ and CH—(C₁-C₃-alkyl); C independently has the samemeaning as B; R⁵ is a group Ar or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: halogens;pseudohalogens; NH₂; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, C₁-C₁₀-alkoxy,(C₁-C₁₀-alkyl)amino, and di(C₁-C₁₀-alkyl)amino, the substituents ofwhich are chosen from F, OH, C₁-C₈-alkoxy, aryloxy,(C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;aryl-substituted C₁-C₄-alkyl; heteroaryl-substitued C₁-C₄-alkyl; CF₃;NO₂; OH; phenoxy; benzyloxy; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH;phenylamino; benzylamino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR²⁴R²⁵; R²⁶SO₂NH—; R²⁷SO₂N(C₁-C₆-alkyl)-; andsaturated and at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms chosen from N, O,and S, which heterocycles can be substituted by one or more substituentschosen from halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, andwherein said heterocycles can optionally be condensed to said group Aror said group Hetar; and wherein all aryl, heteroaryl, phenyl,aryl-containing, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said group Ar orsaid group Hetar, can be substituted by one or more substituents chosenfrom halogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;R⁶ is chosen from: H; C₁-C₁₀-alkyl, which can be substituted by one ormore substituents chosen from F, C₁-C₈-alkoxy, and di(C₁-C₈-alkyl)amino;aryl-(C₁-C₄-alkyl) and heteroaryl-(C₁-C₄-alkyl), which can besubstituted by one or more substituents chosen from halogens,C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino; R⁷ is chosen from: H;C₁-C₁₀-alkyl which can be substituted by one or more substituents chosenfrom F, C₁-C₈-alkoxy, di(C₁-C₈-alkyl)amino and phenyl; phenyl; indanyl;and heteroaryl; and wherein each of the aforementioned aromatic groupscan be unsubstituted or carry one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁸ is H orC₁-C₁₀-alkyl; R⁹ is chosen from: C₁-C₁₀-alkyl which can be unsubstitutedor carry one or more substituents chosen from: F, (C₁-C₄)-alkoxy,di(C₁-C₃-alkyl)amino; and unsubstituted and at least monosubstitutedphenyl and heteroaryl, the substituents of which are chosen fromC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃; R¹⁰independently has the same meaning as R⁷; R¹¹ independently has the samemeaning as R⁸; R¹² independently has the same meaning as R⁶; R¹³ ischosen from: H; C₁-C₆-alkyl; unsubstituted and substituted phenyl,benzyl, heteroaryl, (C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁴ independently has the same meaning asR¹³; R¹⁵ is chosen from: H; C₁-C₁₀-alkyl; (C₁-C₃-alkoxy)-C₁-C₃-alkyl;and substituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁶ is chosen from: C₁-C₁₀-alkyl which canbe substituted by one or more substituents chosen from F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, (C₁-C₈-alkyl)amino anddi(C₁-C₈-alkyl)amino; CF₃; and substituted and unsubstituted phenyl andheteroaryl, the substituents of which are chosen from halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one ormore of these substitutents can be present; R¹⁷ independently has thesame meaning as R⁷; R¹⁸ independently has the same meaning as R⁸; R¹⁹independently has the same meaning as R¹⁶; R²⁰ independently has thesame meaning as R¹⁶; R²¹ independently has the same meaning as R⁶; R²²independently has the same meaning as R⁷; R²³ independently has the samemeaning as R⁸; R²⁴ independently has the same meaning as R⁷; R²⁵independently has the same meaning as R⁸; R²⁶ independently has the samemeaning as R¹⁶; R²⁷ independently has the same meaning as R¹⁶;heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S:the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;aryl is phenyl, naphth-1-yl or naphth-2-yl; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0, 1 or 2; wherein thephysiologically active amount of the compound according to the generalformula (I) in any of its stereoisomeric forms or a mixture thereof inany ratio or a pharmaceutically acceptable salt thereof stimulates theexpression of endothelial NO-synthase in the mammal.
 16. A method oftreating a mammal suffering from diabetes complications wherein thediabetes complications are chosen from nephropathy and retinopathy,which method comprises administering to said mammal a physiologicallyactive amount of a compound according to the general formula (I), in anyof its stereoisomeric forms or a mixture thereof in any ratio or apharmaceutically acceptable salt thereof

wherein, in the formula (I), R¹ and R⁴ are independently from each otherchosen from: H; unsubstituted and at least monosubstituted C₁-C₁₀-alkyl,C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents of which are chosenfrom F, OH, C₁-C₈-alkoxy, (C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃;R⁹CO; CONR¹⁰R¹¹; COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵;S(O)_(m)R₁₆; SO₂NR¹⁷R¹⁸; and NO₂; R² and R³ are independently from eachother chosen from: H; halogens; pseudohalogens; unsubstituted and atleast monosubstituted C₁-C₁₀-alkyl the substituents of which are chosenfrom OH, phenyl, and heteroaryl; OH; C₁-C₁₀-alkoxy; phenoxy;S(O)_(m)R¹⁹; CF₃; CN; NO₂; (C₁-C₁₀-alkyl)amino; di(C₁-C₁₀-alkyl)amino;(C₁-C₆-alkyl)-CONH—; unsubstituted and at least monosubstitutedphenyl-CONH— and phenyl-SO₂—O—, the substituents of which are chosenfrom halogens, pseudohalogens, CH₃ and methoxy; (C₁-C₆-alkyl)SO₂—O—;unsubstituted and at least monosubstituted (C₁-C₆-alkyl)CO, thesubstituents of which are chosen from F, di(C₁-C₃-alkyl)amino,pyrrolidinyl and piperidinyl; and phenyl-CO, the phenyl part of whichcan be substituted by one or more substituents chosen from C₁-C₃-alkyl,halogens and methoxy; A is chosen from CH₂, CHOH and CH—(C₁-C₃-alkyl); Bis chosen from CH₂ and CH—(C₁-C₃-alkyl); C independently has the samemeaning as B; R⁵ is a group Ar or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: halogens;pseudohalogens; NH₂; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, C₁-C₁₀-alkoxy,(C₁-C₁₀-alkyl)amino, and di(C₁-C₁₀-alkyl)amino, the substituents ofwhich are chosen from F, OH, C₁-C₈-alkoxy, aryloxy,(C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;aryl-substituted C₁-C₄-alkyl; heteroaryl-substituted C₁-C₂-alkyl; CF₃;NO₂; OH; phenoxy; benzyloxy; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH;phenylamino; benzylamino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR²⁴R²⁵; R²⁶SO₂NH—; R²⁷SO₂N(C₁-C₆-alkyl)-; andsaturated and at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms chosen from N, O,and S, which heterocycles can be substituted by one or more substituentschosen from halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, andwherein said heterocycles can optionally be condensed to said group Aror said group Hetar; and wherein all aryl, heteroaryl, phenyl,aryl-containing, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said group Ar orsaid group Hetar, can be substituted by one or more substituents chosenfrom halogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;R⁶ is chosen from: H; C₁-C₁₀-alkyl, which can be substituted by one ormore substituents chosen from F, C₁-C₈-alkoxy, and di(C₁-C₈-alkyl)amino;aryl-(C₁-C₄-alkyl) and heteroaryl-(C₁-C₄-alkyl), which can besubstituted by one or more substituents chosen from halogens,C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino; R⁷ is chosen from: H;C₁-C₁₀-alkyl which can be substituted by one or more substituents chosenfrom F, C₁-C₈-alkoxy, di(C₁-C₈-alkyl)amino and phenyl; phenyl; indanyl;and heteroaryl; and wherein each of the aforementioned aromatic groupscan be unsubstituted or carry one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁸ is H orC₁-C₁₀-alkyl; R⁹ is chosen from: C₁-C₁₀-alkyl which can be unsubstitutedor carry one or more substituents chosen from: F, (C₁-C₄)-alkoxy,di(C₁-C₃-alkyl)amino; and unsubstituted and at least monosubstitutedphenyl and heteroaryl, the substituents of which are chosen fromC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃; R¹⁰independently has the same meaning as R⁷; R¹¹ independently has the samemeaning as R⁸; R¹² independently has the same meaning as R⁶; R¹³ ischosen from: H; C₁-C₆-alkyl; unsubstituted and substituted phenyl,benzyl, heteroaryl, (C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁴ independently has the same meaning asR¹³; R¹⁵ is chosen from: H; C₁-C₁₀-alkyl; (C₁-C₃-alkoxy)-C₁-C₃-alkyl;and substituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁶ is chosen from: C₁-C₁₀-alkyl which canbe substituted by one or more substituents chosen from F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, (C₁-C₈-alkyl)amino anddi(C₁-C₈-alkyl)amino; CF₃; and substituted and unsubstituted phenyl andheteroaryl, the substituents of which are chosen from halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one ormore of these substitutents can be present; R¹⁷ independently has thesame meaning as R⁷; R¹⁸ independently has the same meaning as R⁸; R¹⁹independently has the same meaning as R¹⁶; R²⁰ independently has thesame meaning as R¹⁶; R²¹ independently has the same meaning as R⁶; R²²independently has the same meaning as R⁷; R²³ independently has the samemeaning as R⁸; R²⁴ independently has the same meaning as R⁷; R²⁵independently has the same meaning as R⁸; R²⁶ independently has the samemeaning as R¹⁶; R²⁷ independently has the same meaning as R¹⁶;heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;aryl is phenyl, naphth-1-yl or naphth-2-yl; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0, 1 or 2; wherein thephysiologically active amount of the compound according to the generalformula (I) in any of its stereoisomeric forms or a mixture thereof inany ratio or a pharmaceutically acceptable salt thereof stimulates theexpression of endothelial NO-synthase in the mammal.
 17. A method oflowering cardiovascular risk of postmenopausal women and mammalscontraceptives, which method comprises administering to said mammal aphysiologically active amount of a compound according to the generalformula (I), in any of its stereoisomeric forms or a mixture thereof inany ratio or a pharmaceutically acceptable salt thereof

wherein, in the formula (I), R¹ and R⁴ are independently from each otherchosen from: H; unsubstituted and at least monosubstituted C₁-C₁₀-alkyl,C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents of which are chosenfrom F, OH, C₁-C₈-alkoxy, (C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃;R⁹CO; CONR¹⁰R¹¹; COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵;S(O)_(m)R₁₆; SO₂NR¹⁷R¹⁸; and NO₂; R² and R³ are independently from eachother chosen from: H; halogens; pseudohalogens; unsubstituted and atleast monosubstituted C₁-C₁₀-alkyl the substituents of which are chosenfrom OH, phenyl, and heteroaryl; OH; C₁-C₁₀-alkoxy; phenoxy;S(O)_(m)R¹⁹; CF₃; CN; NO₂; (C₁-C₁₀-alkyl)amino; di(C₁-C₁₀-alkyl)amino;(C₁-C₆-alkyl)-CONH—; unsubstituted and at least monosubstitutedphenyl-CONH— and phenyl-SO₂—O—, the substituents of which are chosenfrom halogens, pseudohalogens, CH₃ and methoxy; (C₁-C₆-alkyl)SO₂—O—;unsubstituted and at least monosubstituted (C₁-C₆-alkyl)CO, thesubstituents of which are chosen from F, di(C₁-C₃-alkyl)amino,pyrrolidinyl and piperidinyl; and phenyl-CO, the phenyl part of whichcan be substituted by one or more substituents chosen from C₁-C₃-alkyl,halogens and methoxy; A is chosen from CH₂, CHOH and CH—(C₁-C₃-alkyl); Bis chosen from CH₂ and CH—(C₁-C₃-alkyl); C independently has the samemeaning as B; R⁵ is a group Ar or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: halogens;pseudohalogens; NH₂; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, C₁-C₁₀-alkoxy,(C₁-C₁₀-alkyl)amino, and di(C₁-C₁₀-alkyl)amino, the substituents ofwhich are chosen from F, OH, C₁-C₈-alkoxy, aryloxy,(C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;aryl-substituted C₁-C₄-alkyl; heteroaryl-substituted C₁-C₂-alkyl; CF₃;NO₂; OH; phenoxy; benzyloxy; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH;phenylamino; benzylamino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR²⁴R²⁵; R²⁶SO₂NH—; R²⁷SO₂N(C₁-C₆-alkyl)-; andsaturated and at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms chosen from N, O,and S, which heterocycles can be substituted by one or more substituentschosen from halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, andwherein said heterocycles can optionally be condensed to said group Aror said group Hetar; and wherein all aryl, heteroaryl, phenyl,aryl-containing, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said group Ar orsaid group Hetar, can be substituted by one or more substituents chosenfrom halogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;R⁶ is chosen from: H; C₁-C₁₀-alkyl, which can be substituted by one ormore substituents chosen from F, C₁-C₈-alkoxy, and di(C₁-C₈-alkyl)amino;aryl-(C₁-C₄-alkyl) and heteroaryl-(C₁-C₄-alkyl), which can besubstituted by one or more substituents chosen from halogens,C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino; R⁷ is chosen from: H;C₁-C₁₀-alkyl which can be substituted by one or more substituents chosenfrom F, C₁-C₈-alkoxy, di(C₁-C₈-alkyl)amino and phenyl; phenyl; indanyl;and heteroaryl; and wherein each of the aforementioned aromatic groupscan be unsubstituted or carry one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁸ is H orC₁-C₁₀-alkyl; R⁹ is chosen from: C₁-C₁₀-alkyl which can be unsubstitutedor carry one or more substituents chosen from: F, (C₁-C₄)-alkoxy,di(C₁-C₃-alkyl)amino; and unsubstituted and at least monosubstitutedphenyl and heteroaryl, the substituents of which are chosen fromC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃; R¹⁰independently has the same meaning as R⁷; R¹¹ independently has the samemeaning as R⁸; R¹² independently has the same meaning as R⁶; R¹³ ischosen from: H; C₁-C₆-alkyl; unsubstituted and substituted phenyl,benzyl, heteroaryl, (C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁴ independently has the same meaning asR¹³; R¹⁵ is chosen from: H; C₁-C₁₀-alkyl; (C₁-C₃-alkoxy)-C₁-C₃-alkyl;and substituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁶ is chosen from: C₁-C₁₀-alkyl which canbe substituted by one or more substituents chosen from F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, (C₁-C₈-alkyl)amino anddi(C₁-C₈-alkyl)amino; CF₃; and substituted and unsubstituted phenyl andheteroaryl, the substituents of which are chosen from halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one ormore of these substitutents can be present; R¹⁷ independently has thesame meaning as R⁷; R¹⁸ independently has the same meaning as R⁸; R¹⁹independently has the same meaning as R¹⁶; R²⁰ independently has thesame meaning as R¹⁶; R²¹ independently has the same meaning as R⁶; R²²independently has the same meaning as R⁷; R²³ independently has the samemeaning as R⁸; R²⁴ independently has the same meaning as R⁷; R²⁵independently has the same meaning as R⁸; R²⁶ independently has the samemeaning as R¹⁶; R²⁷ independently has the same meaning as R¹⁶;heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;aryl is phenyl, naphth-1-yl or naphth-2-yl; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0, 1 or 2; wherein thephysiologically active amount of the compound according to the generalformula (I) in any of its stereoisomeric forms or a mixture thereof inany ratio or a pharmaceutically acceptable salt thereof stimulates theexpression of endothelial NO-synthase in the mammal.
 18. A method oftreating a mammal suffering from a cardiovascular disease, which methodcomprises administering to said mammal a physiologically active amountof a compound according to the general formula (I), in any of itsstereoisomeric forms or a mixture thereof in any ratio or apharmaceutically acceptable salt thereof

wherein, in the formula (I), R¹ and R⁴ are independently from each otherchosen from: H; unsubstituted and at least monosubstituted C₁-C₁₀-alkyl,C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents of which are chosenfrom F, OH, C₁-C₈-alkoxy, (C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃;R⁹CO; CONR¹⁰R¹¹; COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵;S(O)_(m)R₁₆; SO₂NR¹⁷R¹⁸; and NO₂; R² and R³ are independently from eachother chosen from: H; halogens; pseudohalogens; unsubstituted and atleast monosubstituted C₁-C₁₀-alkyl the substituents of which are chosenfrom OH, phenyl, and heteroaryl; OH; C₁-C₁₀-alkoxy; phenoxy;S(O)_(m)R¹⁹; CF₃; CN; NO₂; (C₁-C₁₀-alkyl)amino; di(C₁-C₁₀-alkyl)amino;(C₁-C₆-alkyl)-CONH—; unsubstituted and at least monosubstitutedphenyl-CONH— and phenyl-SO₂—O—, the substituents of which are chosenfrom halogens, pseudohalogens, CH₃ and methoxy; (C₁-C₆-alkyl)SO₂—O—;unsubstituted and at least monosubstituted (C₁-C₆-alkyl)CO, thesubstituents of which are chosen from F, di(C₁-C₃-alkyl)amino,pyrrolidinyl and piperidinyl; and phenyl-CO, the phenyl part of whichcan be substituted by one or more substituents chosen from C₁-C₃-alkyl,halogens and methoxy; A is chosen from CH₂, CHOH and CH—(C₁-C₃-alkyl); Bis chosen from CH₂ and CH—(C₁-C₃-alkyl); C independently has the samemeaning as B; R⁵ is a group Ar or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: halogens;pseudohalogens; NH₂; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, C₁-C₁₀-alkoxy,(C₁-C₁₀-alkyl)amino, and di(C₁-C₁₀-alkyl)amino, the substituents ofwhich are chosen from F, OH, C₁-C₈-alkoxy, aryloxy,(C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;aryl-substituted C₁-C₄-alkyl; heteroaryl-substituted C₁-C₂-alkyl; CF₃;NO₂; OH; phenoxy; benzyloxy; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH;phenylamino; benzylamino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR²⁴R²⁵; R²⁶SO₂NH—; R²⁷SO₂N(C₁-C₆-alkyl)-; andsaturated and at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms chosen from N, O,and S, which heterocycles can be substituted by one or more substituentschosen from halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, andwherein said heterocycles can optionally be condensed to said group Aror said group Hetar; and wherein all aryl, heteroaryl, phenyl,aryl-containing, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said group Ar orsaid group Hetar, can be substituted by one or more substituents chosenfrom halogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;R⁶ is chosen from: H; C₁-C₁₀-alkyl, which can be substituted by one ormore substituents chosen from F, C₁-C₈-alkoxy, and di(C₁-C₈-alkyl)amino;aryl-(C₁-C₄-alkyl) and heteroaryl-(C₁-C₄-alkyl), which can besubstituted by one or more substituents chosen from halogens,C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino; R⁷ is chosen from: H;C₁-C₁₀-alkyl which can be substituted by one or more substituents chosenfrom F, C₁-C₈-alkoxy, di(C₁-C₈-alkyl)amino and phenyl; phenyl; indanyl;and heteroaryl; and wherein each of the aforementioned aromatic groupscan be unsubstituted or carry one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁸ is H orC₁-C₁₀-alkyl; R⁹ is chosen from: C₁-C₁₀-alkyl which can be unsubstitutedor carry one or more substituents chosen from: F, (C₁-C₄)-alkoxy,di(C₁-C₃-alkyl)amino; and unsubstituted and at least monosubstitutedphenyl and heteroaryl, the substituents of which are chosen fromC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃; R¹⁰independently has the same meaning as R⁷; R¹¹ independently has the samemeaning as R⁸; R¹² independently has the same meaning as R⁶; R¹³ ischosen from: H; C₁-C₆-alkyl; unsubstituted and substituted phenyl,benzyl, heteroaryl, (C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁴ independently has the same meaning asR¹³; R¹⁵ is chosen from: H; C₁-C₁₀-alkyl; (C₁-C₃-alkoxy)-C₁-C₃-alkyl;and substituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁶ is chosen from: C₁-C₁₀-alkyl which canbe substituted by one or more substituents chosen from F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, (C₁-C₈-alkyl)amino anddi(C₁-C₈-alkyl)amino; CF₃; and substituted and unsubstituted phenyl andheteroaryl, the substituents of which are chosen from halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one ormore of these substitutents can be present; R¹⁷ independently has thesame meaning as R⁷; R¹⁸ independently has the same meaning as R⁸; R¹⁹independently has the same meaning as R¹⁶; R²⁰ independently has thesame meaning as R¹⁶; R²¹ independently has the same meaning as R⁶; R²²independently has the same meaning as R⁷; R²³ independently has the samemeaning as R⁸; R²⁴ independently has the same meaning as R⁷; R²⁵independently has the same meaning as R⁸; R²⁶ independently has the samemeaning as R¹⁶; R²⁷ independently has the same meaning as R¹⁶;heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;aryl is phenyl, naphth-1-yl or naphth-2-yl; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0, 1 or 2; wherein thephysiologically active amount of the compound according to the generalformula (I) in any of its stereoisomeric forms or a mixture thereof inany ratio or a pharmaceutically acceptable salt thereof stimulates theexpression of endothelial NO-synthase in the mammal.
 19. The methodaccording to claim 18, wherein the compound of the general formula (I)is chosen from compounds of the general formula (I), wherein R¹ ischosen from: H; C₁-C₄-alkyl; C₁-C₄-alkoxy; CF₃; halogens;pseudohalogens; (C₁-C₄-alkyl)-S(O)_(m)—; and unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃,and wherein heteroaryl is chosen from 5- and 6-membered heterocyclescontaining one or more heteroatoms chosen from N, O, and S; R² and R³are independently from each other chosen from: H; halogens;pseudohalogens; and C₁-C₃-alkyl; R⁴ independently has the same meaningas R¹; A is chosen from CH₂ and CHOH; B and C are independently fromeach other chosen from CH₂ and CH—CH₃; R⁵ is a group Ar or a group Hetarboth of which can be unsubstituted or carry one or more substituentschosen from: halogens; CN; NH₂; unsubstituted and at leastmonosubstituted C₁-C₈-alkyl, C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₁-C₈-alkoxy,(C₁-C₈-alkyl)amino, and di(C₁-C₈-alkyl)amino, the substituents of whichare chosen from F, C₁-C₆-alkoxy, phenoxy, (C₁-C₆-alkyl)mercapto, NH₂,(C₁-C₆-alkyl)amino, and di(C₁-C₆-alkyl)amino; C₃-C₅-alkandiyl; phenyl;heteroaryl; phenyl-substituted C₁-C₂-alkyl; heteroaryl-substitutedC₁-C₂-alkyl; CF₃; OH; phenoxy; benzyloxy; (C₁-C₆-alkyl)COO;S(O)_(m)(C₁-C₆)-alkyl; S(O)_(m)-phenyl; S(O)_(m)-heteroaryl; SH;phenylamino; benzylamino; (C₁-C₆-alkyl)-CONH—;(C₁-C₆-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—; phenyl-CON(C₁-C₄-alkyl)-;heteroaryl-CONH—; heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₆-alkyl)-CO;phenyl-CO; heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—;—CH₂CH₂O—; COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₆-alkyl);—CON(di(C₁-C₆-alkyl)); CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₆-alkyl);—SO₂NH(phenyl); —SO₂N(di(C₁-C₆-alkyl)); (C₁-C₆-alkyl)SO₂NH—;(C₁-C₆-alkyl)SO₂N(C₁-C₆-alkyl)-; phenyl-SO₂NH—;phenyl-SO₂N(C₁-C₆-alkyl)-; heteroaryl-SO₂NH—;heteroaryl-SO₂N(C₁-C₆-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, and wherein saidheterocycles can optionally be condensed to said group Ar or said groupHetar; and wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said group Ar or said group Hetar, can be substituted byone or more substituents chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one ormore heteroatoms chosen from N, O, and S; the group Hetar is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one ormore heteroatoms chosen from N, O, and S; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0 or
 2. 20. The method according toclaim 18, wherein the compound according to of the general formula (I)is chosen from compounds of the general formula (I), wherein R¹ is H,halogen, or C₁-C₄-alkyl; R² and R³ are each H; R⁴ independently has thesame meaning as R¹; A is CH₂; R⁵ is phenyl or a group Hetar both ofwhich can be unsubstituted or carry one or more substituents chosenfrom: halogens; CN; NH₂; unsubstituted and at least monosubstitutedC₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₃-alkoxy,(C₁-C₄-alkyl)amino, and di(C₁-C₄-alkyl)amino, the substituents of whichare chosen from F, C₁-C₃-alkoxy, (C₁-C₃-alkyl)mercapto, and NH₂;C₃-C₅-alkandryl; phenyl; heteroaryl; phenyl-substituted C₁-C₂-alkyl;heteroaryl-substituted C₁-C₂-alkyl; CF₃; OH; (C₁-C₄-alkyl)COO;S(O)_(m)(C₁-C₄)-alkyl; (C₁-C₄-alkyl)-CONH—;(C₁-C₄-alkyl)-CON(C₁-C₄-alkyl)-; (C₁-C₄-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—;COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl));CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂NH(phenyl);—SO₂N(di(C₁-C₄-alkyl)); (C₁-C₄-alkyl)SO₂NH—;(C₁-C₄-alkyl)SO₂N(C₁-C₄-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, and wherein saidheterocycles can optionally be condensed to said phenyl or said groupHetar; and wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said phenyl or said group Hetar, can be substituted byone or more substituents; chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one, twoor three heteroatoms chosen from N, O, and S; the group Hetar is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one, twoor three heteroatoms chosen from N, O, and S; and m is 0 or
 2. 21. Themethod according to claim 18, wherein the compound according to thegeneral formula (I) is chosen from the compounds of the general formula(I) wherein R¹ is H, halogen, or C₁-C₄-alkyl; R² and R³ are each H; R⁴independently has the same meaning as R¹; A and B are each CH₂; C is CH₂or CH—CH₃; R⁵ is phenyl or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: F; Cl; Br;C₁-C₃-alkyl; C₁-C₃-alkoxymethyl; 2-amino-3,3,3-trifluoro-propyl-; CF₃;C₃-C₅-alkandiyl; phenyl; heteroaryl; benzyl; heteroaryl-methyl; OH;C₁-C₃-alkoxy; phenoxy; trifluoromethoxy; 2,2,2-trifluoroethoxy;(C₁-C₄-alkyl)COO; (C₁-C₃-alkyl)mercapto; phenylmercapto;(C₁-C₃-alkyl)sulfonyl; phenylsulfonyl; NH₂; (C₁-C₄-alkyl)amino;di(C₁-C₄-alkyl)amino; (C₁-C₃-alkyl)-CONH—; (C₁-C₃-alkyl)-SO₂NH—;(C₁-C₃-alkyl)-CO; phenyl-CO; —OCH₂O—; —OCF₂O—; —CH₂CH₂O—;COO(C₁-C₄-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl)); CN;—SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂N(di(C₁-C₄-alkyl)); pyrrolidinyl;piperidinyl; morpholinyl; and thiomorpholinyl; and wherein allheteroaryl, phenyl, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said phenyl or saidgroup Hetar, can be substituted by one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;heteroaryl is chosen from: furyl, pyrrolyl, thienyl, thiazolyl,isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl,pyrazinyl, pyridyl, pyrimidinyl, benzoimidazolyl, benzothiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl,indolyl, benzofuranyl, benzothiophenyl, and indazolyl; the group Hetaris chosen from: furyl, pyrrolyl, thienyl, thiazolyl, isothiazolyl,oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl, pyrazinyl,pyridyl, pyrimidinyl, benzoimidazolyl, benzothiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl, indolyl,benzofuranyl, benzothiophenyl, and indazolyl.
 22. The method accordingto claim 18, wherein the compound according to the general formula (I)is chosen from the compounds of the general formula (I) wherein R¹ is H,halogen or C₁-C₄-alkyl; R² and R³ are each H; R⁴ independently has thesame meaning as R¹; A and B are each CH₂; C is CH₂ or CH—CH₃; R⁵ ischosen from: 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl,4-(C₁-C₃-alkoxy)-phenyl, 4-trifluoromethoxyphenyl,2-bromo-4-fluorophenyl, 2-chloro-4-fluorophenyl, 3,4-dimethylphenyl,2,4-dimethylphenyl, 4-chloro-2-methylphenyl, 2-hydroxy-4-methylphenyl,2-hydroxy-4-ethoxyphenyl, 2-methoxy-4-methylphenyl, 4-phenoxyphenyl,3-fluoro-4-methylphenyl, benzo[1,3]dioxol-5-yl,2,2-difluoro-benzo[1,3]dioxol-5-yl, 2,3-dihydrobenzofuran-5-yl,1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-yl,1-(4-fluoro-phenyl)-3,5-dimethyl-1H-pyrazole-4-yl,1H-benzotriazole-5-yl, 1H-indole-4-yl, 1H-indole-6-yl,1-isopropyl-2-trifluoromethyl-1H-benzoimidazole-5-yl,1-methyl-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-yl,1-phenyl-5-trifluoromethyl-1H-pyrazole-4-yl,2-(2-hydroxy-pyridin-4-yl)-1H-benzoimidazole-5-yl,2-(4-cyano-phenyl)-1H-benzoimidazole-5-yl, 2,4-dimethyl-oxazole-5-yl,2,4-dimethyl-pyrimidine-5-yl, 2,4-dimethyl-thiazole-5-yl,2,5-dimethyl-1H-pyrrole-3-yl, 2,5-dimethyl-1-phenyl-1H-pyrrole-3-yl,2,5-dimethyl-1-pyridin-4-ylmethyl-1H-pyrrolyl,2,5-dimethyl-2H-pyrazole-3-yl, 2,6-dichloro-pyrid-3-yl,2,6-dimethoxy-pyrid-3-yl, 2,6-dimethyl-pyrid-3-yl,2-amino-4,6-dimethyl-pyrid-3-yl, 2-amino-6-chloro-pyrid-3-yl,2-amino-pyrid-3-yl, 2-chloro-6-methyl-pyrid-3-yl, 2-chloro-pyrid-4-yl,2-cyclopropyl-4-methyl-thiazole-5-yl,2-dimethylamino-4-methyl-thiazole-5-yl, 2-dimethylamino-pyrid-4-yl,2-ethyl-5-methyl-2H-pyrazole-3-yl, 2-hydroxy-6-methyl-pyrid-3-yl,2-methyl-1H-benzoimidazole-5-yl, 2-methyl-3H-benzoimidazole-5-yl,2-methyl-pyrid-3-yl, 2-methyl-6-trifluoromethyl-pyrid-3-yl,2-methyl-thiazole-5-yl, 2-morpholin-4-yl-pyridin-4-yl,2-morpholin-4-yl-pyrimidine-5-yl, 2-pyrrolidin-1-yl-pyridin-4-yl,3,5-dimethyl-1H-pyrazole-4-yl, 3-amino-5,6-dimethyl-pyrazine-2-yl,3-amino-5-methyl-pyrazine-2-yl, 3-amino-pyrazine-2-yl,3-dimethylamino-4-methyl-phenyl, 3-dimethylamino-phenyl,3H-benzoimidazole-5-yl, 1H-benzoimidazole-5-yl,3-methanesulfonylamino-2-methyl-phenyl, 3-methanesulfonylamino-phenyl,3-methyl-isoxazole-4-yl, 3-morpholin-4-yl-phenyl,3-piperidin-1-yl-phenyl, 3-pyrrolidin-1-yl-phenyl,4-(2,2,2-trifluoro-ethoxy)-phenyl, 4,6-dimethyl-pyrid-3-yl,4-amino-2-ethyl sulfanyl-pyrimidine-5-yl,4-amino-2-methyl-pyrimidine-5-yl,4-chloro-3-methanesulfonylamino-phenyl, 4-chloro-3-sulfamoyl-phenyl,4-methyl-3-methylamino-phenyl, 4-methyl-thiazole-5-yl, pyridine-2-yl,pyridine-3-yl, pyridine-4-yl, 5-thiophen-2-yl-pyrid-3-yl,2-methyl-4-trifluoromethyl-thiazol-5-yl,5,6,7,8-tetrahydro-quinoline-3-yl, 5-amino-1-phenyl-1H-pyrazole-4-yl,5-methanesulfonyl-2-methyl-phenyl, 5-methyl-1-phenyl-1H-pyrazole-4-yl,5-methyl-isoxazole-3-yl, 5-methyl-pyrid-3-yl, 5-methyl-pyrazine-2-yl,6-chloro-pyrid-3-yl, 6-cyano-pyrid-3-yl, 6-dimethylamino-pyrid-3-yl,6-ethynyl-pyrid-3-yl, 6-methoxymethyl-pyrid-3-yl, 6-methoxy-pyrid-3-yl,6-methyl-2-methylamino-pyrid-3-yl, 6-methylamino-pyrazine-2-yl,6-methyl-pyrid-3-yl, 6-morpholin-4-yl-pyrid-3-yl,6-pyrrolidin-1-yl-pyrid-3-yl, imidazo[1,2-a]pyridine-2-yl,6-trifluoromethyl-pyrid-3-yl, and pyrimidine-4-yl.
 23. The methodaccording to claim 18, wherein the mammal is a human.
 24. A method oftreating a mammal suffering from a disease chosen from stable andunstable angina pectoris, coronary heart disease, Prinzmetal angina,acute coronary syndrome, heart failure, myocardial infarction, stroke,thrombosis, peripheral artery occlusive disease, endothelialdysfunction, atherosclerosis, restenosis, endothelial damage after PTCA,hypertension, chronic glomerulonephritis, erectile dysfunction,ventricular arrhythmia, diabetes, diabetes complications, angiogenesis,asthma bronchiale, chronic renal failure, cirrhosis of the liver,osteoporosis, diseases with symptoms of restricted memory performanceand/or a restricted ability to learn, which method comprisesadministering to said mammal a physiologically active amount of acompound according to the general formula (I), in any of itsstereoisomeric forms or a mixture thereof in any ratio or apharmaceutically acceptable salt thereof

wherein R¹ is H, halogen or C₁-C₄-alkyl; R² and R³ are each H; R⁴independently has the same meaning as R¹; A and B are each CH₂; C is CH₂or CH—CH₃; R⁵ is chosen from: benzo[1,3]dioxol-5-yl,2,2-difluoro-benzo[1,3]dioxol-5-yl, 2,3-dihydrobenzofuran-5-yl,1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-yl,1-(4-fluoro-phenyl)-3,5-dimethyl-1H-pyrazole-4-yl,1H-benzotriazole-5-yl, 1H-indole-4-yl, 1H-indole-6-yl,1-isopropyl-2-trifluoromethyl-1H-benzoimidazole-5-yl,1-methyl-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-yl,1-phenyl-5-trifluoromethyl-1H-pyrazole-4-yl,2-(2-hydroxy-pyridin-4-yl)-1H-benzoimidazole-5-yl,2-(4-cyano-phenyl)-1H-benzoimidazole-5-yl, 2,4-dimethyl-oxazole-5-yl,2,4-dimethyl-pyrimidine-5-yl, 2,4-dimethyl-thiazole-5-yl,2,5-dimethyl-1H-pyrrole-3-yl, 2,5-dimethyl-1-phenyl-1H-pyrrole-3-yl,2,5-dimethyl-1-pyridin-4-ylmethyl-1H-pyrrolyl,2,5-dimethyl-2H-pyrazole-3-yl, 2,6-dichloro-pyrid-3-yl,2,6-dimethoxy-pyrid-3-yl, 2,6-dimethyl-pyrid-3-yl,2-amino-4,6-dimethyl-pyrid-3-yl, 2-amino-6-chloro-pyrid-3-yl,2-amino-pyrid-3-yl, 2-chloro-6-methyl-pyrid-3-yl, 2-chloro-pyrid-4-yl,2-cyclopropyl-4-methyl-thiazole-5-yl,2-dimethylamino-4-methyl-thiazole-5-yl, 2-dimethylamino-pyrid-4-yl,2-ethyl-5-methyl-2H-pyrazole-3-yl, 2-hydroxy-6-methyl-pyrid-3-yl,2-methyl-1H-benzoimidazole-5-yl, 2-methyl-3H-benzoimidazole-5-yl,2-methyl-pyrid-3-yl, 2-methyl-6-trifluoromethyl-pyrid-3-yl,2-methyl-thiazole-5-yl, 2-morpholin-4-yl-pyridin-4-yl,2-morpholin-4-yl-pyrimidine-5-yl, 2-pyrrolidin-1-yl-pyridin-4-yl,3,5-dimethyl-1H-pyrazole-4-yl, 3-amino-5,6-dimethyl-pyrazine-2-yl,3-amino-5-methyl-pyrazine-2-yl, 3-amino-pyrazine-2-yl,3H-benzoimidazole-5-yl, 1H-benzoimidazole-5-yl, 3-methyl-isoxazole-4-yl,4,6-dimethyl-pyrid-3-yl, 4-amino-2-ethylsulfanyl-pyrimidine-5-yl,4-amino-2-methyl-pyrimidine-5-yl, 4-methyl-thiazole-5-yl, pyridine-2-yl,pyridine-3-yl, pyridine-4-yl, 5-thiophen-2-yl-pyrid-3-yl,2-methyl-4-trifluoromethyl-thiazol-5-yl,5,6,7,8-tetrahydro-quinoline-3-yl, 5-amino-1-phenyl-1H-pyrazole-4-yl,5-methyl-1-phenyl-1H-pyrazole-4-yl, 5-methyl-isoxazole-3-yl,5-methyl-pyrid-3-yl, 5-methyl-pyrazine-2-yl, 6-chloro-pyrid-3-yl,6-cyano-pyrid-3-yl, 6-dimethylamino-pyrid-3-yl, 6-ethynyl-pyrid-3-yl,6-methoxymethyl-pyrid-3-yl, 6-methoxy-pyrid-3-yl,6-methyl-2-methylamino-pyrid-3-yl, 6-methylamino-pyrazine-2-yl,6-methyl-pyrid-3-yl, 6-morpholin-4-yl-pyrid-3-yl,6-pyrrolidin-1-yl-pyrid-3-yl, imidazo[1,2-a]pyridine-2-yl,6-trifluoromethyl-pyrid-3-yl, and pyrimidine-4-yl.
 25. The methodaccording to claim 24, wherein the hypertension is chosen from essentialhypertension, pulmonary hypertension, secondary hypertension, andrenovascular hypertension.
 26. The method according to claim 24, whereinthe diabetes complications are chosen from nephropathy and retinopathy.27. The method according to claim 24, which method lowers cardiovascularrisk of postmenopausal women and mammals taking contraceptives.
 28. Themethod according to claim 24, wherein the mammal is a human.
 29. Amethod of treating a mammal suffering from a cardiovascular disease,which method comprises administering to said mammal a physiologicallyactive amount of a compound according to the general formula (I), in anyof its stereoisomeric forms or a mixture thereof in any ratio or apharmaceutically acceptable salt thereof

wherein R¹ is H, halogen or C₁-C₄-alkyl; R² and R³ are each H; R⁴independently has the same meaning as R¹; A and B are each CH₂; C is CH₂or CH—CH₃; R⁵ is chosen from: benzo[1,3]dioxol-5-yl,2,2-difluoro-benzo[1,3]dioxol-5-yl, 2,3-dihydrobenzofuran-5-yl,1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-yl,1-(4-fluoro-phenyl)-3,5-dimethyl-1H-pyrazole-4-yl,1H-benzotriazole-5-yl, 1H-indole-4-yl, 1H-indole-6-yl,1-isopropyl-2-trifluoromethyl-1H-benzoimidazole-5-yl,1-methyl-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-yl,1-phenyl-5-trifluoromethyl-1H-pyrazole-4-yl,2-(2-hydroxy-pyridin-4-yl)-1H-benzoimidazole-5-yl,2-(4-cyano-phenyl)-1H-benzoimidazole-5-yl, 2,4-dimethyl-oxazole-5-yl,2,4-dimethyl-pyrimidine-5-yl, 2,4-dimethyl-thiazole-5-yl,2,5-dimethyl-1H-pyrrole-3-yl, 2,5-dimethyl-1-phenyl-1H-pyrrole-3-yl,2,5-dimethyl-1-pyridin-4-ylmethyl-1H-pyrrolyl,2,5-dimethyl-2H-pyrazole-3-yl, 2,6-dichloro-pyrid-3-yl,2,6-dimethoxy-pyrid-3-yl, 2,6-dimethyl-pyrid-3-yl,2-amino-4,6-dimethyl-pyrid-3-yl, 2-amino-6-chloro-pyrid-3-yl,2-amino-pyrid-3-yl, 2-chloro-6-methyl-pyrid-3-yl, 2-chloro-pyrid-4-yl,2-cyclopropyl-4-methyl-thiazole-5-yl,2-dimethylamino-4-methyl-thiazole-5-yl, 2-dimethylamino-pyrid-4-yl,2-ethyl-5-methyl-2H-pyrazole-3-yl, 2-hydroxy-6-methyl-pyrid-3-yl,2-methyl-1H-benzoimidazole-5-yl, 2-methyl-3H-benzoimidazole-5-yl,2-methyl-pyrid-3-yl, 2-methyl-6-trifluoromethyl-pyrid-3-yl,2-methyl-thiazole-5-yl, 2-morpholin-4-yl-pyridin-4-yl,2-morpholin-4-yl-pyrimidine-5-yl, 2-pyrrolidin-1-yl-pyridin-4-yl,3,5-dimethyl-1H-pyrazole-4-yl, 3-amino-5,6-dimethyl-pyrazine-2-yl,3-amino-5-methyl-pyrazine-2-yl, 3-amino-pyrazine-2-yl,3H-benzoimidazole-5-yl, 1H-benzoimidazole-5-yl, 3-methyl-isoxazole-4-yl,4,6-dimethyl-pyrid-3-yl, 4-amino-2-ethylsulfanyl-pyrimidine-5-yl,4-amino-2-methyl-pyrimidine-5-yl, 4-methyl-thiazole-5-yl, pyridine-2-yl,pyridine-3-yl, pyridine-4-yl, 5-thiophen-2-yl-pyrid-3-yl,2-methyl-4-trifluoromethyl-thiazol-5-yl,5,6,7,8-tetrahydro-quinoline-3-yl, 5-amino-1-phenyl-1H-pyrazole-4-yl,5-methyl-1-phenyl-1H-pyrazole-4-yl, 5-methyl-isoxazole-3-yl,5-methyl-pyrid-3-yl, 5-methyl-pyrazine-2-yl, 6-chloro-pyrid-3-yl,6-cyano-pyrid-3-yl, 6-dimethylamino-pyrid-3-yl, 6-ethynyl-pyrid-3-yl,6-methoxymethyl-pyrid-3-yl, 6-methoxy-pyrid-3-yl,6-methyl-2-methylamino-pyrid-3-yl, 6-methylamino-pyrazine-2-yl,6-methyl-pyrid-3-yl, 6-morpholin-4-yl-pyrid-3-yl,6-pyrrolidin-1-yl-pyrid-3-yl, imidazo[1,2-a]pyridine-2-yl,6-trifluoromethyl-pyrid-3-yl, and pyrimidine-4-yl.
 30. The methodaccording to claim 29, wherein the mammal is a human.
 31. A method oftreating a mammal suffering from a disease chosen from stable andunstable angina pectoris, coronary heart disease, acute coronarysyndrome, heart failure, myocardial infarction, thrombosis, peripheralartery occlusive disease, endothelial dysfunction, atherosclerosis,restenosis, endothelial damage after PTCA, hypertension, andosteoporosis, which method comprises administering to said mammal aphysiologically active amount of a compound according to the generalformula (I), in any of its stereoisomeric forms or a mixture thereof inany ratio or a pharmaceutically acceptable salt thereof

wherein, in the formula (I), R¹ and R⁴ are independently from each otherchosen from: H; unsubstituted and at least monosubstituted C₁-C₁₀-alkyl,C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents of which are chosenfrom F, OH, C₁-C₈-alkoxy, (C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃;R⁹CO; CONR¹⁰R¹¹; COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵;S(O)_(m)R₁₆; SO₂NR¹⁷R¹⁸; and NO₂; R² and R³ are independently from eachother chosen from: H; halogens; pseudohalogens; unsubstituted and atleast monosubstituted C₁-C₁₀-alkyl the substituents of which are chosenfrom OH, phenyl, and heteroaryl; OH; C₁-C₁₀-alkoxy; phenoxy;S(O)_(m)R¹⁹; CF₃; CN; NO₂; (C₁-C₁₀-alkyl)amino; di(C₁-C₁₀-alkyl)amino;(C₁-C₆-alkyl)-CONH—; unsubstituted and at least monosubstitutedphenyl-CONH— and phenyl-SO₂—O—, the substituents of which are chosenfrom halogens, pseudohalogens, CH₃ and methoxy; (C₁-C₆-alkyl)SO₂—O—;unsubstituted and at least monosubstituted (C₁-C₆-alkyl)CO, thesubstituents of which are chosen from F, di(C₁-C₃-alkyl)amino,pyrrolidinyl and piperidinyl; and phenyl-CO, the phenyl part of whichcan be substituted by one or more substituents chosen from C₁-C₃-alkyl,halogens and methoxy; A is chosen from CH₂, CHOH and CH—(C₁-C₃-alkyl); Bis chosen from CH₂ and CH—(C₁-C₃-alkyl); C independently has the samemeaning as B; R⁵ is a group Ar or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: halogens;pseudohalogens; NH₂; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, C₁-C₁₀-alkoxy,(C₁-C₁₀-alkyl)amino, and di(C₁-C₁₀-alkyl)amino, the substituents ofwhich are chosen from F, OH, C₁-C₈-alkoxy, aryloxy,(C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;aryl-substituted C₁-C₄-alkyl; heteroaryl-substituted C₁-C₂-alkyl; CF₃;NO₂; OH; phenoxy; benzyloxy; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH;phenylamino; benzylamino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₃O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR²⁴R²⁵; R²⁶SO₃NH—; R²⁷SO₃N(C₁-C₆-alkyl)-; andsaturated and at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms chosen from N, O,and S, which heterocycles can be substituted by one or more substituentschosen from halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, andwherein said heterocycles can optionally be condensed to said group Aror said group Hetar; and wherein all aryl, heteroaryl, phenyl,aryl-containing, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said group Ar orsaid group Hetar, can be substituted by one or more substituents chosenfrom halogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;R⁶ is chosen from: H; C₁-C₁₀-alkyl, which can be substituted by one ormore substituents chosen from F, C₁-C₈-alkoxy, and di(C₁-C₈-alkyl)amino;aryl-(C₁-C₄-alkyl) and heteroaryl-(C₁-C₄-alkyl), which can besubstituted by one or more substituents chosen from halogens,C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino; R⁷ is chosen from: H;C₁-C₁₀-alkyl which can be substituted by one or more substituents chosenfrom F, C₁-C₈-alkoxy, di(C₁-C₈-alkyl)amino and phenyl; phenyl; indanyl;and heteroaryl; and wherein each of the aforementioned aromatic groupscan be unsubstituted or carry one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁸ is H orC₁-C₁₀-alkyl; R⁹ is chosen from: C₁-C₁₀-alkyl which can be unsubstitutedor carry one or more substituents chosen from: F, (C₁-C₄)-alkoxy,di(C₁-C₃-alkyl)amino; and unsubstituted and at least monosubstitutedphenyl and heteroaryl, the substituents of which are chosen fromC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃; R¹⁰independently has the same meaning as R⁷; R¹¹ independently has the samemeaning as R⁸; R¹² independently has the same meaning as R⁶; R¹³ ischosen from: H; C₁-C₆-alkyl; unsubstituted and substituted phenyl,benzyl, heteroaryl, (C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁴ independently has the same meaning asR¹³; R¹⁵ is chosen from: H; C₁-C₁₀-alkyl; (C₁-C₃-alkoxy)-C₁-C₃-alkyl;and substituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁶ is chosen from: C₁-C₁₀-alkyl which canbe substituted by one or more substituents chosen from F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, (C₁-C₈-alkyl)amino anddi(C₁-C₈-alkyl)amino; CF₃; and substituted and unsubstituted phenyl andheteroaryl, the substituents of which are chosen from halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one ormore of these substitutents can be present; R¹⁷ independently has thesame meaning as R⁷; R¹⁸ independently has the same meaning as R⁸; R¹⁹independently has the same meaning as R¹⁶; R²⁰ independently has thesame meaning as R¹⁶; R²¹ independently has the same meaning as R⁶; R²²independently has the same meaning as R⁷; R²³ independently has the samemeaning as R⁸; R²⁴ independently has the same meaning as R⁷; R²⁵independently has the same meaning as R⁸; R²⁶ independently has the samemeaning as R¹⁶; R²⁷ independently has the same meaning as R¹⁶;heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;aryl is phenyl, naphth-1-yl or naphth-2-yl; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0, 1 or
 2. 32. The method accordingto claim 31, wherein the compound according to the general formula (I)is chosen from compounds of the general formula (I), wherein R¹ ischosen from: H; C₁-C₄-alkyl; C₁-C₄-alkoxy; CF₃; halogens;pseudohalogens; (C₁-C₄-alkyl)-S(O)_(m)—; and unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃,and wherein heteroaryl is chosen from 5- and 6-membered heterocyclescontaining one or more heteroatoms chosen from N, O, and S; R² and R³are independently from each other chosen from: H; halogens;pseudohalogens; and C₁-C₃-alkyl; R⁴ independently has the same meaningas R¹; A is chosen from CH₂ and CHOH; B and C are independently fromeach other chosen from CH₂ and CH—CH₃; R⁵ is a group Ar or a group Hetarboth of which can be unsubstituted or carry one or more substituentschosen from: halogens; CN; NH₂; unsubstituted and at leastmonosubstituted C₁-C₈-alkyl, C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₁-C₈-alkoxy,(C₁-C₈-alkyl)amino, and di(C₁-C₈-alkyl)amino, the substituents of whichare chosen from F, C₁-C₆-alkoxy, phenoxy, (C₁-C₆-alkyl)mercapto, NH₂,(C₁-C₆-alkyl)amino, and di(C₁-C₆-alkyl)amino; C₃-C₅-alkandiyl; phenyl;heteroaryl; phenyl-substituted C₁-C₂-alkyl; CF₃; OH; phenoxy; benzyloxy;(C₁-C₆-alkyl)COO; S(O)_(m)(C₁-C₆)-alkyl; S(O)_(m)-phenyl;S(O)_(m)-heteroaryl; SH; phenylamino; benzylamino; (C₁-C₆-alkyl)-CONH—;(C₁-C₆-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—; phenyl-CON(C₁-C₄-alkyl)-;heteroaryl-CONH—; heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₆-alkyl)-CO;phenyl-CO; heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—;—CH₂CH₂O—; COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₆-alkyl);—CON(di(C₁-C₆-alkyl)); CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₆-alkyl);—SO₂NH(phenyl); —SO₂N(di(C₁-C₆-alkyl)); (C₁-C₆-alkyl)SO₂NH—;(C₁-C₆-alkyl)SO₂N(C₁-C₆-alkyl)-; phenyl-SO₂NH—;phenyl-SO₂N(C₁-C₆-alkyl)-; heteroaryl-SO₂NH—;heteroaryl-SO₂N(C₁-C₆-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, and wherein saidheterocycles can optionally be condensed to said group Ar or said groupHetar; and wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said group Ar or said group Hetar, can be substituted byone or more substituents chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one ormore heteroatoms chosen from N, O, and S; the group Hetar is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one ormore heteroatoms chosen from N, O, and S; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0 or
 2. 33. The method according toclaim 31, wherein the compound according to the general formula (I) ischosen from the compounds of the general formula (I), wherein R¹ is H,halogen, or C₁-C₄-alkyl; R² and R³ are each H; R⁴ independently has thesame meaning as R¹; A is CH₂; R⁵ is phenyl or a group Hetar both ofwhich can be unsubstituted or carry one or more substituents chosenfrom: halogens; CN; NH₂; unsubstituted and at least monosubstitutedC₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₃-alkoxy,(C₁-C₄-alkyl)amino, and di(C₁-C₄-alkyl)amino, the substituents of whichare chosen from F, C₁-C₃-alkoxy, (C₁-C₃-alkyl)mercapto, and NH₂;C₃-C₅-alkandiyl; phenyl; heteroaryl; phenyl-substituted C₁-C₂-alkyl;heteroaryl-substituted C₁-C₂-alkyl; CF₃; OH; (C₁-C₄-alkyl)COO;S(O)_(m)(C₁-C₄)-alkyl; (C₁-C₄-alkyl)-CONH—;(C₁-C₄-alkyl)-CON(C₁-C₄-alkyl)-; (C₁-C₄-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—;COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl));CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂NH(phenyl);—SO₂N(di(C₁-C₄-alkyl)); (C₁-C₄-alkyl)SO₂NH—;(C₁-C₄-alkyl)SO₂N(C₁-C₄-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, and wherein saidheterocycles can optionally be condensed to said phenyl or said groupHetar; and wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said phenyl or said group Hetar, can be substituted byone or more substituents; chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one, twoor three heteroatoms chosen from N, O, and S; the group Hetar is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one, twoor three heteroatoms chosen from N, O, and S; and m is 0 or
 2. 34. Themethod according to claim 31, wherein the compound according to thegeneral formula (I) is chosen from the compounds of the general formula(I) wherein R¹ is H, halogen, or C₁-C₄-alkyl; R² and R³ are each H; R⁴independently has the same meaning as R¹; A and B are each CH₂; C is CH₂or CH—CH₃; R⁵ is phenyl or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: F; Cl; Br;C₁-C₃-alkyl; C₁-C₃-alkoxymethyl; 2-amino-3,3,3-trifluoro-propyl-; CF₃;C₃-C₅-alkandiyl; phenyl; heteroaryl; benzyl; heteroaryl-methyl; OH;C₁-C₃-alkoxy; phenoxy; trifluoromethoxy; 2,2,2-trifluoroethoxy;(C₁-C₄-alkyl)COO; (C₁-C₃-alkyl)mercapto; phenylmercapto;(C₁-C₃-alkyl)sulfonyl; phenylsulfonyl; NH₂; (C₁-C₄-alkyl)amino;di(C₁-C₄-alkyl)amino; (C₁-C₃-alkyl)-CONH—; (C₁-C₃-alkyl)-SO₂NH—;(C₁-C₃-alkyl)-CO; phenyl-CO; —OCH₂O—; —OCF₂O—; —CH₂CH₂O—;COO(C₁-C₄-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl)); CN;—SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂N(di(C₁-C₄-alkyl)); pyrrolidinyl;piperidinyl; morpholinyl; and thiomorpholinyl; and wherein allheteroaryl, phenyl, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said phenyl or saidgroup Hetar, can be substituted by one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;heteroaryl is chosen from: furyl, pyrrolyl, thienyl, thiazolyl,isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl,pyrazinyl, pyridyl, pyrimidinyl, benzoimidazolyl, benzothiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl,indolyl, benzofuranyl, benzothiophenyl, and indazolyl; the group Hetaris chosen from: furyl, pyrrolyl, thienyl, thiazolyl, isothiazolyl,oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl, pyrazinyl,pyridyl, pyrimidinyl, benzoimidazolyl, benzothiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl, indolyl,benzofuranyl, benzothiophenyl, and indazolyl.
 35. The method accordingto claim 31, wherein the compound according to the general formula (I)is chosen from the compounds of the general formula (I) wherein R¹ is H,halogen or C₁-C₄-alkyl; R² and R³ are each H; R⁴ independently has thesame meaning as R¹; A and B are each CH₂; C is CH₃ or CH—CH₃; R⁵ ischosen from: 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl,4-(C₁-C₃-alkoxy)-phenyl, 4-trifluoromethoxyphenyl,2-bromo-4-fluorophenyl, 2-chloro-4-fluorophenyl, 3,4-dimethylphenyl,2,4-dimethylphenyl, 4-chloro-2-methylphenyl, 2-hydroxy-4-methylphenyl,2-hydroxy-4-ethoxyphenyl, 2-methoxy-4-methylphenyl, 4-phenoxyphenyl,3-fluoro-4-methylphenyl, benzo[1,3]dioxol-5-yl,2,2-difluoro-benzo[1,3]dioxol-5-yl, 2,3-dihydrobenzofuran-5-yl,1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-yl,1-(4-fluoro-phenyl)-3,5-dimethyl-1H-pyrazole-4-yl,1H-benzotriazole-5-yl, 1H-indole-4-yl, 1H-indole-6-yl,1-isopropyl-2-trifluoromethyl-1H-benzoimidazole-5-yl,1-methyl-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-yl,1-phenyl-5-trifluoromethyl-1H-pyrazole-4-yl,2-(2-hydroxy-pyridin-4-yl)-1H-benzoimidazole-5-yl,2-(4-cyano-phenyl)-1H-benzoimidazole-5-yl, 2,4-dimethyl-oxazole-5-yl,2,4-dimethyl-pyrimidine-5-yl, 2,4-dimethyl-thiazole-5-yl,2,5-dimethyl-1H-pyrrole-3-yl, 2,5-dimethyl-1-phenyl-1H-pyrrole-3-yl,2,5-dimethyl-1-pyridin-4-ylmethyl-1H-pyrrolyl,2,5-dimethyl-2H-pyrazole-3-yl, 2,6-dichloro-pyrid-3-yl,2,6-dimethoxy-pyrid-3-yl, 2,6-dimethyl-pyrid-3-yl,2-amino-4,6-dimethyl-pyrid-3-yl, 2-amino-6-chloro-pyrid-3-yl,2-amino-pyrid-3-yl, 2-chloro-6-methyl-pyrid-3-yl, 2-chloro-pyrid-4-yl,2-cyclopropyl-4-methyl-thiazole-5-yl,2-dimethylamino-4-methyl-thiazole-5-yl, 2-dimethylamino-pyrid-4-yl,2-ethyl-5-methyl-2H-pyrazole-3-yl, 2-hydroxy-6-methyl-pyrid-3-yl,2-methyl-1H-benzoimidazole-5-yl, 2-methyl-3H-benzoimidazole-5-yl,2-methyl-pyrid-3-yl, 2-methyl-6-trifluoromethyl-pyrid-3-yl,2-methyl-thiazole-5-yl, 2-morpholin-4-yl-pyridin-4-yl,2-morpholin-4-yl-pyrimidine-5-yl, 2-pyrrolidin-1-yl-pyridin-4-yl,3,5-dimethyl-1H-pyrazole-4-yl, 3-amino-5,6-dimethyl-pyrazine-2-yl,3-amino-5-methyl-pyrazine-2-yl, 3-amino-pyrazine-2-yl,3-dimethylamino-4-methyl-phenyl, 3-dimethylamino-phenyl,3H-benzoimidazole-5-yl, 1H-benzoimidazole-5-yl,3-methanesulfonylamino-2-methyl-phenyl, 3-methanesulfonylamino-phenyl,3-methyl-isoxazole-4-yl, 3-morpholin-4-yl-phenyl,3-piperidin-1-yl-phenyl, 3-pyrrolidin-1-yl-phenyl,4-(2,2,2-trifluoro-ethoxy)-phenyl, 4,6-dimethyl-pyrid-3-yl,4-amino-2-ethyl sulfanyl-pyrimidine-5-yl,4-amino-2-methyl-pyrimidine-5-yl,4-chloro-3-methanesulfonylamino-phenyl, 4-chloro-3-sulfamoyl-phenyl,4-methyl-3-methylamino-phenyl, 4-methyl-thiazole-5-yl, pyridine-2-yl,pyridine-3-yl, pyridine-4-yl, 5-thiophen-2-yl-pyrid-3-yl,2-methyl-4-trifluoromethyl-thiazol-5-yl,5,6,7,8-tetrahydro-quinoline-3-yl, 5-amino-1-phenyl-1H-pyrazole-4-yl,5-methanesulfonyl-2-methyl-phenyl, 5-methyl-1-phenyl-1H-pyrazole-4-yl,5-methyl-isoxazole-3-yl, 5-methyl-pyrid-3-yl, 5-methyl-pyrazine-2-yl,6-chloro-pyrid-3-yl, 6-cyano-pyrid-3-yl, 6-dimethylamino-pyrid-3-yl,6-ethynyl-pyrid-3-yl, 6-methoxymethyl-pyrid-3-yl, 6-methoxy-pyrid-3-yl,6-methyl-2-methylamino-pyrid-3-yl, 6-methylamino-pyrazine-2-yl,6-methyl-pyrid-3-yl, 6-morpholin-4-yl-pyrid-3-yl,6-pyrrolidin-1-yl-pyrid-3-yl, imidazo[1,2-a]pyridine-2-yl,6-trifluoromethyl-pyrid-3-yl, and pyrimidine-4-yl.
 36. The methodaccording to claim 31, wherein the mammal is a human.
 37. A method oftreating a mammal suffering from a cardiovascular disease, which methodcomprises administering to said mammal a physiologically active amountof a compound according to the general formula (I), in any of itsstereoisomeric forms or a mixture thereof in any ratio or apharmaceutically acceptable salt thereof

wherein, in the formula (I), R¹ and R⁴ are independently from each otherchosen from: H; unsubstituted and at least monosubstituted C₁-C₁₀-alkyl,C₂-C₁₀-alkenyl and C₂-C₁₀-alkynyl, the substituents of which are chosenfrom F, OH, C₁-C₈-alkoxy, (C₁-C₈-alkyl)mercapto, CN, COOR⁶, CONR⁷R⁸, andunsubstituted and at least monosubstituted phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃;R⁹CO; CONR¹⁰R¹¹; COOR¹²; CF₃; halogens; pseudohalogens; NR¹³R¹⁴; OR¹⁵;S(O)_(m)R₁₆; SO₂NR¹⁷R¹⁸; and NO₂; R² and R³ are independently from eachother chosen from: H; halogens; pseudohalogens; unsubstituted and atleast monosubstituted C₁-C₁₀-alkyl the substituents of which are chosenfrom OH, phenyl, and heteroaryl; OH; C₁-C₁₀-alkoxy; phenoxy;S(O)_(m)R¹⁹; CF₃; CN; NO₂; (C₁-C₁₀-alkyl)amino; di(C₁-C₁₀-alkyl)amino;(C₁-C₆-alkyl)-CONH—; unsubstituted and at least monosubstitutedphenyl-CONH— and phenyl-SO₂—O—, the substituents of which are chosenfrom halogens, pseudohalogens, CH₃ and methoxy; (C₁-C₆-alkyl)SO₂—O—;unsubstituted and at least monosubstituted (C₁-C₆-alkyl)CO, thesubstituents of which are chosen from F, di(C₁-C₃-alkyl)amino,pyrrolidinyl and piperidinyl; and phenyl-CO, the phenyl part of whichcan be substituted by one or more substituents chosen from C₁-C₃-alkyl,halogens and methoxy; A is chosen from CH₂, CHOH and CH—(C₁-C₃-alkyl); Bis chosen from CH₂ and CH—(C₁-C₃-alkyl); C independently has the samemeaning as B; R⁵ is a group Ar or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: halogens;pseudohalogens; NH₂; unsubstituted and at least monosubstitutedC₁-C₁₀-alkyl, C₂-C₁₀-alkenyl, C₂-C₁₀-alkynyl, C₁-C₁₀-alkoxy,(C₁-C₁₀-alkyl)amino, and di(C₁-C₁₀-alkyl)amino, the substituents ofwhich are chosen from F, OH, C₁-C₈-alkoxy, aryloxy,(C₁-C₈-alkyl)mercapto, NH₂, (C₁-C₈-alkyl)amino, anddi(C₁-C₈-alkyl)amino; C₃-C₅-alkandiyl; phenyl; heteroaryl;aryl-substituted C₁-C₄-alkyl; heteroaryl-substituted C₁-C₂-alkyl; CF₃;NO₂; OH; phenoxy; benzyloxy; (C₁-C₁₀-alkyl)COO; S(O)_(m)R²⁰; SH;phenylamino; benzylamino; (C₁-C₁₀-alkyl)-CONH—;(C₁-C₁₀-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—;phenyl-CON(C₁-C₄-alkyl)-; heteroaryl-CONH—;heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₁₀-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—; COOR²¹;CONR²²R²³; CNH(NH₂); SO₂NR²⁴R²⁵; R²⁶SO₂NH—; R²⁷SO₂N(C₁-C₆-alkyl)-; andsaturated and at least monounsaturated aliphatic, mononuclear 5- to7-membered heterocycles containing 1 to 3 heteroatoms chosen from N, O,and S, which heterocycles can be substituted by one or more substituentschosen from halogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, andwherein said heterocycles can optionally be condensed to said group Aror said group Hetar; and wherein all aryl, heteroaryl, phenyl,aryl-containing, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said group Ar orsaid group Hetar, can be substituted by one or more substituents chosenfrom halogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;R⁶ is chosen from: H; C₁-C₁₀-alkyl, which can be substituted by one ormore substituents chosen from F, C₁-C₈-alkoxy, and di(C₁-C₈-alkyl)amino;aryl-(C₁-C₄-alkyl) and heteroaryl-(C₁-C₄-alkyl), which can besubstituted by one or more substituents chosen from halogens,C₁-C₄-alkoxy, and di(C₁-C₆-alkyl)amino; R⁷ is chosen from: H;C₁-C₁₀-alkyl which can be substituted by one or more substituents chosenfrom F, C₁-C₈-alkoxy, di(C₁-C₈-alkyl)amino and phenyl; phenyl; indanyl;and heteroaryl; and wherein each of the aforementioned aromatic groupscan be unsubstituted or carry one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃; R⁸ is H orC₁-C₁₀-alkyl; R⁹ is chosen from: C₁-C₁₀-alkyl which can be unsubstitutedor carry one or more substituents chosen from: F, (C₁-C₄)-alkoxy,di(C₁-C₃-alkyl)amino; and unsubstituted and at least monosubstitutedphenyl and heteroaryl, the substituents of which are chosen fromC₁-C₃-alkyl, C₁-C₃-alkoxy, halogens, pseudohalogens, and CF₃; R¹⁰independently has the same meaning as R⁷; R¹¹ independently has the samemeaning as R⁸; R¹² independently has the same meaning as R⁶; R¹³ ischosen from: H; C₁-C₆-alkyl; unsubstituted and substituted phenyl,benzyl, heteroaryl, (C₁-C₆-alkyl)-CO, phenyl-CO, and heteroaryl-CO, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁴ independently has the same meaning asR¹³; R¹⁵ is chosen from: H; C₁-C₁₀-alkyl; (C₁-C₃-alkoxy)-C₁-C₃-alkyl;and substituted and unsubstituted benzyl, phenyl and heteroaryl, thesubstituents of which are chosen from halogens, pseudohalogens,C₁-C₃-alkyl, C₁-C₃-alkoxy, and CF₃, and wherein one or more of thesesubstituents can be present; R¹⁶ is chosen from: C₁-C₁₀-alkyl which canbe substituted by one or more substituents chosen from F, OH,C₁-C₈-alkoxy, aryloxy, (C₁-C₈-alkyl)mercapto, (C₁-C₈-alkyl)amino anddi(C₁-C₈-alkyl)amino; CF₃; and substituted and unsubstituted phenyl andheteroaryl, the substituents of which are chosen from halogens,pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃, and wherein one ormore of these substitutents can be present; R¹⁷ independently has thesame meaning as R⁷; R¹⁸ independently has the same meaning as R⁸; R¹⁹independently has the same meaning as R¹⁶; R²⁰ independently has thesame meaning as R¹⁶; R²¹ independently has the same meaning as R⁶; R²²independently has the same meaning as R⁷; R²³ independently has the samemeaning as R⁸; R²⁴ independently has the same meaning as R⁷; R²⁵independently has the same meaning as R⁸; R²⁶ independently has the samemeaning as R¹⁶; R²⁷ independently has the same meaning as R¹⁶;heteroaryl is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;the group Hetar is a 5 to 10-membered, aromatic, mono- or bicyclicheterocycle containing one or more heteroatoms chosen from N, O, and S;aryl is phenyl, naphth-1-yl or naphth-2-yl; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0, 1 or
 2. 38. The method accordingto claim 37, wherein the compound according to the general formula (I)is chosen from compounds of the general formula (I), wherein R¹ ischosen from: H; C₁-C₄-alkyl; C₁-C₄-alkoxy; CF₃; halogens;pseudohalogens; (C₁-C₄-alkyl)-S(O)_(m)—; and unsubstituted and at leastmonosubstituted phenyl and heteroaryl, the substituents of which arechosen from halogens, pseudohalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy and CF₃,and wherein heteroaryl is chosen from 5- and 6-membered heterocyclescontaining one or more heteroatoms chosen from N, O, and S; R² and R³are independently from each other chosen from: H; halogens;pseudohalogens; and C₁-C₃-alkyl; R⁴ independently has the same meaningas R¹; A is chosen from CH₂ and CHOH; B and C are independently fromeach other chosen from CH₂ and CH—CH₃; R⁵ is a group Ar or a group Hetarboth of which can be unsubstituted or carry one or more substituentschosen from: halogens; CN; NH₂; unsubstituted and at leastmonosubstituted C₁-C₈-alkyl, C₂-C₈-alkenyl, C₂-C₈-alkynyl, C₁-C₈-alkoxy,(C₁-C₈-alkyl)amino, and di(C₁-C₈-alkyl)amino, the substituents of whichare chosen from F, C₁-C₆-alkoxy, phenoxy, (C₁-C₆-alkyl)mercapto, NH₂,(C₁-C₆-alkyl)amino, and di(C₁-C₆-alkyl)amino; C₃-C₅-alkandiyl; phenyl;heteroaryl; phenyl-substituted C₁-C₂-alkyl; heteroaryl-substitutedC₁-C₂-alkyl; CF₃; OH; phenoxy; benzyloxy; (C₁-C₆-alkyl)COO;S(O)_(m)(C₁-C₆)-alkyl; S(O)_(m)-phenyl; S(O)_(m)-heteroaryl; SH;phenylamino; benzylamino; (C₁-C₆-alkyl)-CONH—;(C₁-C₆-alkyl)-CON(C₁-C₄-alkyl)-; phenyl-CONH—; phenyl-CON(C₁-C₄-alkyl)-;heteroaryl-CONH—; heteroaryl-CON(C₁-C₄-alkyl)-; (C₁-C₆-alkyl)-CO;phenyl-CO; heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—;—CH₂CH₂O—; COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₆-alkyl);—CON(di(C₁-C₆-alkyl)); CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₆-alkyl);—SO₂NH(phenyl); —SO₂N(di(C₁-C₆-alkyl)); (C₁-C₆-alkyl)SO₂NH—;(C₁-C₆-alkyl)SO₂N(C₁-C₆-alkyl)-; phenyl-SO₂NH—;phenyl-SO₂N(C₁-C₆-alkyl)-; heteroaryl-SO₂NH—;heteroaryl-SO₂N(C₁-C₆-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, and wherein saidheterocycles can optionally be condensed to said group Ar or said groupHetar; and wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said group Ar or said group Hetar, can be substituted byone or more substituents chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one ormore heteroatoms chosen from N, O, and S; the group Hetar is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one ormore heteroatoms chosen from N, O, and S; the group Ar is phenyl,naphth-1-yl or naphth-2-yl; and m is 0 or
 2. 39. The method according toclaim 37, wherein the compound according to the general formula (I) ischosen from the compounds of the general formula (I), wherein R¹ is H,halogen, or C₁-C₄-alkyl; R² and R³ are each H; R⁴ independently has thesame meaning as R¹; A is CH₂; R⁵ is phenyl or a group Hetar both ofwhich can be unsubstituted or carry one or more substituents chosenfrom: halogens; CN; NH₂; unsubstituted and at least monosubstitutedC₁-C₆-alkyl, C₂-C₆-alkenyl, C₂-C₆-alkynyl, C₁-C₃-alkoxy,(C₁-C₄-alkyl)amino, and di(C₁-C₄-alkyl)amino, the substituents of whichare chosen from F, C₁-C₃-alkoxy, (C₁-C₃-alkyl)mercapto, and NH₂;C₃-C₅-alkandiyl; phenyl; heteroaryl; phenyl-substituted C₁-C₂-alkyl;CF₃; OH; (C₁-C₄-alkyl)COO; S(O)_(m)(C₁-C₄)-alkyl; (C₁-C₄-alkyl)-CONH—;(C₁-C₄-alkyl)-CON(C₁-C₄-alkyl)-; (C₁-C₄-alkyl)-CO; phenyl-CO;heteroaryl-CO; CF₃—CO; —OCH₂O—; —OCF₂O—; —OCH₂CH₂O—; —CH₂CH₂O—;COO(C₁-C₆-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl));CNH(NH₂); —SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂NH(phenyl);—SO₂N(di(C₁-C₄-alkyl)); (C₁-C₄-alkyl)SO₂NH—;(C₁-C₄-alkyl)SO₂N(C₁-C₄-alkyl)-; and saturated and at leastmonounsaturated aliphatic, mononuclear 5- to 7-membered heterocyclescontaining 1 to 3 heteroatoms chosen from N, O, and S, whichheterocycles can be substituted by one or more substituents chosen fromhalogens, C₁-C₃-alkyl, C₁-C₃-alkoxy, OH, oxo and CF₃, and wherein saidheterocycles can optionally be condensed to said phenyl or said groupHetar; and wherein all heteroaryl, phenyl, heteroaryl-containing andphenyl-containing groups, which are optionally present in saidsubstituents of said phenyl or said group Hetar, can be substituted byone or more substituents; chosen from halogens, pseudohalogens,C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃; heteroaryl is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one, twoor three heteroatoms chosen from N, O, and S; the group Hetar is a 5 to10-membered, aromatic, mono- or bicyclic heterocycle containing one, twoor three heteroatoms chosen from N, O, and S; and m is 0 or
 2. 40. Themethod according to claim 37, wherein the compound according to thegeneral formula (I) is chosen from the compounds of the general formula(I) wherein R¹ is H, halogen, or C₁-C₄-alkyl; R² and R³ are each H; R⁴independently has the same meaning as R¹; A and B are each CH₂; C is CH₂or CH—CH₃; R⁵ is phenyl or a group Hetar both of which can beunsubstituted or carry one or more substituents chosen from: F; Cl; Br;C₁-C₃-alkyl; C₁-C₃-alkoxymethyl; 2-amino-3,3,3-trifluoro-propyl-; CF₃;C₃-C₅-alkandiyl; phenyl; heteroaryl; benzyl; heteroaryl-methyl; OH;C₁-C₃-alkoxy; phenoxy; trifluoromethoxy; 2,2,2-trifluoroethoxy;(C₁-C₄-alkyl)COO; (C₁-C₃-alkyl)mercapto; phenylmercapto;(C₁-C₃-alkyl)sulfonyl; phenylsulfonyl; NH₂; (C₁-C₄-alkyl)amino;di(C₁-C₄-alkyl)amino; (C₁-C₃-alkyl)-CONH—; (C₁-C₃-alkyl)-SO₂NH—;(C₁-C₃-alkyl)-CO; phenyl-CO; —OCH₂O—; —OCF₂O—; —CH₂CH₂O—;COO(C₁-C₄-alkyl); —CONH₂; —CONH(C₁-C₄-alkyl); —CON(di(C₁-C₄-alkyl)); CN;—SO₂NH₂; —SO₂NH(C₁-C₄-alkyl); —SO₂N(di(C₁-C₄-alkyl)); pyrrolidinyl;piperidinyl; morpholinyl; and thiomorpholinyl; and wherein allheteroaryl, phenyl, heteroaryl-containing and phenyl-containing groups,which are optionally present in said substituents of said phenyl or saidgroup Hetar, can be substituted by one or more substituents chosen fromhalogens, pseudohalogens, C₁-C₃-alkyl, OH, C₁-C₃-alkoxy, and CF₃;heteroaryl is chosen from: furyl, pyrrolyl, thienyl, thiazolyl,isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl,pyrazinyl, pyridyl, pyrimidinyl, benzoimidazolyl, benzothiazolyl,benzoxazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl,indolyl, benzofuranyl, benzothiophenyl, and indazolyl; the group Hetaris chosen from: furyl, pyrrolyl, thienyl, thiazolyl, isothiazolyl,oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridazinyl, pyrazinyl,pyridyl, pyrimidinyl, benzoimidazolyl, benzothiazolyl, benzoxazolyl,quinolinyl, isoquinolinyl, quinoxalinyl, quinazolyl, indolyl,benzofuranyl, benzothiophenyl, and indazolyl.
 41. The method accordingto claim 37, wherein the compound according to the general formula (I)is chosen from the compounds of the general formula (I) wherein R¹ is H,halogen or C₁-C₄-alkyl; R² and R³ are each H; R⁴ independently has thesame meaning as R¹; A and B are each CH₂; C is CH₂ or CH—CH₃; R⁵ ischosen from: 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl,4-(C₁-C₃-alkoxy)-phenyl, 4-trifluoromethoxyphenyl,2-bromo-4-fluorophenyl, 2-chloro-4-fluorophenyl, 3,4-dimethylphenyl,2,4-dimethylphenyl, 4-chloro-2-methylphenyl, 2-hydroxy-4-methylphenyl,2-hydroxy-4-ethoxyphenyl, 2-methoxy-4-methylphenyl, 4-phenoxyphenyl,3-fluoro-4-methylphenyl, benzo[1,3]dioxol-5-yl,2,2-difluoro-benzo[1,3]dioxol-5-yl, 2,3-dihydrobenzofuran-5-yl,1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-yl,1-(4-fluoro-phenyl)-3,5-dimethyl-1H-pyrazole-4-yl,1H-benzotriazole-5-yl, 1H-indole-4-yl, 1H-indole-6-yl,1-isopropyl-2-trifluoromethyl-1H-benzoimidazole-5-yl,1-methyl-3-oxo-1,2,3,4-tetrahydro-quinoxaline-6-yl,1-phenyl-5-trifluoromethyl-1H-pyrazole-4-yl,2-(2-hydroxy-pyridin-4-yl)-1H-benzoimidazole-5-yl,2-(4-cyano-phenyl)-1H-benzoimidazole-5-yl, 2,4-dimethyl-oxazole-5-yl,2,4-dimethyl-pyrimidine-5-yl, 2,4-dimethyl-thiazole-5-yl,2,5-dimethyl-1H-pyrrole-3-yl, 2,5-dimethyl-1-phenyl-1H-pyrrole-3-yl,2,5-dimethyl-1-pyridin-4-ylmethyl-1H-pyrrolyl,2,5-dimethyl-2H-pyrazole-3-yl, 2,6-dichloro-pyrid-3-yl,2,6-dimethoxy-pyrid-3-yl, 2,6-dimethyl-pyrid-3-yl,2-amino-4,6-dimethyl-pyrid-3-yl, 2-amino-6-chloro-pyrid-3-yl,2-amino-pyrid-3-yl, 2-chloro-6-methyl-pyrid-3-yl, 2-chloro-pyrid-4-yl,2-cyclopropyl-4-methyl-thiazole-5-yl,2-dimethylamino-4-methyl-thiazole-5-yl, 2-dimethylamino-pyrid-4-yl,2-ethyl-5-methyl-2H-pyrazole-3-yl, 2-hydroxy-6-methyl-pyrid-3-yl,2-methyl-1H-benzoimidazole-5-yl, 2-methyl-3H-benzoimidazole-5-yl,2-methyl-pyrid-3-yl, 2-methyl-6-trifluoromethyl-pyrid-3-yl,2-methyl-thiazole-5-yl, 2-morpholin-4-yl-pyridin-4-yl,2-morpholin-4-yl-pyrimidine-5-yl, 2-pyrrolidin-1-yl-pyridin-4-yl,3,5-dimethyl-1H-pyrazole-4-yl, 3-amino-5,6-dimethyl-pyrazine-2-yl,3-amino-5-methyl-pyrazine-2-yl, 3-amino-pyrazine-2-yl,3-dimethylamino-4-methyl-phenyl, 3-dimethylamino-phenyl,3H-benzoimidazole-5-yl, 1H-benzoimidazole-5-yl,3-methanesulfonylamino-2-methyl-phenyl, 3-methanesulfonylamino-phenyl,3-methyl-isoxazole-4-yl, 3-morpholin-4-yl-phenyl,3-piperidin-1-yl-phenyl, 3-pyrrolidin-1-yl-phenyl,4-(2,2,2-trifluoro-ethoxy)-phenyl, 4,6-dimethyl-pyrid-3-yl,4-amino-2-ethyl sulfanyl-pyrimidine-5-yl,4-amino-2-methyl-pyrimidine-5-yl,4-chloro-3-methanesulfonylamino-phenyl, 4-chloro-3-sulfamoyl-phenyl,4-methyl-3-methylamino-phenyl, 4-methyl-thiazole-5-yl, pyridine-2-yl,pyridine-3-yl, pyridine-4-yl, 5-thiophen-2-yl-pyrid-3-yl,2-methyl-4-trifluoromethyl-thiazol-5-yl,5,6,7,8-tetrahydro-quinoline-3-yl, 5-amino-1-phenyl-1H-pyrazole-4-yl,5-methanesulfonyl-2-methyl-phenyl, 5-methyl-1-phenyl-1H-pyrazole-4-yl,5-methyl-isoxazole-3-yl, 5-methyl-pyrid-3-yl, 5-methyl-pyrazine-2-yl,6-chloro-pyrid-3-yl, 6-cyano-pyrid-3-yl, 6-dimethylamino-pyrid-3-yl,6-ethynyl-pyrid-3-yl, 6-methoxymethyl-pyrid-3-yl, 6-methoxy-pyrid-3-yl,6-methyl-2-methylamino-pyrid-3-yl, 6-methylamino-pyrazine-2-yl,6-methyl-pyrid-3-yl, 6-morpholin-4-yl-pyrid-3-yl,6-pyrrolidin-1-yl-pyrid-3-yl, imidazo[1,2-a]pyridine-2-yl,6-trifluoromethyl-pyrid-3-yl, and pyrimidine-4-yl.
 42. The methodaccording to claim 37, wherein the mammal is a human.